Clinical Trials

The objective of the PLATFORM Study is to compare clinical outcomes, resource utilization,
and quality of life (QOL) of FFRCT-guided evaluation versus standard practice evaluation in
patients with suspected CAD in order to further inform patients, health care providers, and
other stakeholders about which technologies are most effective and efficient in the diagnosis
of CAD

Abstract

Chinese translationRandomized trials of coronary artery bypass graft (CABG) surgery and percutaneous coronary intervention (PCI) suggest that patient characteristics modify the effect of treatment on mortality.To assess whether clinical characteristics modify the comparative effectiveness of CABG versus PCI in an unselected, general patient population.Observational treatment comparison using propensity score matching and Cox proportional hazards models.United States, 1992 to 2008.Medicare beneficiaries aged 66 years or older.Multivessel CABG or multivessel PCI.The CABG-PCI hazard ratio (HR) for all-cause mortality, with prespecified treatment-by-covariate interaction tests, and the absolute difference in life-years of survival in clinical subgroups after CABG or PCI, both over 5 years of follow-up.Among 105 156 propensity score-matched patients, CABG was associated with lower mortality than PCI (HR, 0.92 [95% CI, 0.90 to 0.95]; P < 0.001). Association of CABG with lower mortality was significantly greater (interaction P ≤ 0.002 for each) among patients with diabetes (HR, 0.88), a history of tobacco use (HR, 0.82), heart failure (HR, 0.84), and peripheral arterial disease (HR, 0.85). The overall predicted difference in survival between CABG and PCI treatment over 5 years was 0.053 life-years (range, -0.017 to 0.579 life-years). Patients with diabetes, heart failure, peripheral arterial disease, or tobacco use had the largest predicted differences in survival after CABG, whereas those with none of these factors had slightly better survival after PCI.Treatments were chosen by patients and physicians rather than being randomly assigned.Multivessel CABG is associated with lower long-term mortality than multivessel PCI in the community setting. This association is substantially modified by patient characteristics, with improvement in survival concentrated among patients with diabetes, tobacco use, heart failure, or peripheral arterial disease.National Heart, Lung, and Blood Institute.

Abstract

Many myocardial infarctions and strokes occur in individuals with low-density lipoprotein cholesterol levels below recommended treatment thresholds. High sensitivity C-reactive protein (hs-CRP) testing has been advocated to identify low- and intermediate-risk individuals who may benefit from statin therapy.A decision analytic Markov model was used to follow hypothetical cohorts of individuals with normal lipid levels but without coronary artery disease, peripheral arterial disease, or diabetes mellitus. The model compared current Adult Treatment Panel III practice guidelines, a strategy of hs-CRP screening in those without an indication for statin treatment by current practice guidelines followed by treatment only in those with elevated hs-CRP levels, and a strategy of statin therapy at specified predicted risk thresholds without hs-CRP testing. Risk-based treatment without hs-CRP testing was the most cost-effective strategy, assuming that statins were equally effective regardless of hs-CRP status. However, if normal hs-CRP levels identified a subgroup with little or no benefit from statin therapy (<20% relative risk reduction), then hs-CRP screening would be the optimal strategy. If harms from statin use were greater than generally recognized, then use of current clinical guidelines would be the optimal strategy.Risk-based statin treatment without hs-CRP testing is more cost-effective than hs-CRP screening, assuming that statins have good long-term safety and provide benefits among low-risk people with normal hs-CRP.

Abstract

The economic outcomes of clinical management strategies are important in assessing their value to patients.Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) randomized patients with type 2 diabetes mellitus and angiographically documented, stable coronary disease to strategies of (1) prompt revascularization versus medical therapy with delayed revascularization as needed to relieve symptoms and (2) insulin sensitization versus insulin provision. Before randomization, the physician declared whether coronary artery bypass grafting or percutaneous coronary intervention would be used if the patient were assigned to revascularization. We followed 2005 patients for medical utilization and costs and assessed the cost-effectiveness of these management strategies. Medical costs were higher for revascularization than medical therapy, with a significant interaction with the intended method of revascularization (P<0.0001). In the coronary artery bypass grafting stratum, 4-year costs were $80 900 for revascularization versus $60 600 for medical therapy (P<0.0001). In the percutaneous coronary intervention stratum, costs were $73 400 for revascularization versus $67 800 for medical therapy (P<0.02). Costs also were higher for insulin sensitization ($71 300) versus insulin provision ($70 200). Other factors that significantly (P<0.05) and independently increased cost included insulin use and dose at baseline, female sex, white race, body mass index > or =30, and albuminuria. Cost-effectiveness based on 4-year data favored the strategy of medical therapy over prompt revascularization and the strategy of insulin provision over insulin sensitization. Lifetime projections of cost-effectiveness showed that medical therapy was cost-effective compared with revascularization in the percutaneous coronary intervention stratum ($600 per life-year added) with high confidence. Lifetime projections suggest that revascularization may be cost-effective in the coronary artery bypass grafting stratum ($47 000 per life-year added) but with lower confidence.Prompt coronary revascularization significantly increases costs among patients with type 2 diabetes mellitus and stable coronary disease. The strategy of medical therapy (with delayed revascularization as needed) appears to be cost-effective compared with the strategy of prompt coronary revascularization among patients identified a priori as suitable for percutaneous coronary intervention.

Abstract

There is increasing interest in utilizing novel markers of cardiovascular disease risk, and consequently, there is a need to assess the value of their use. This scientific statement reviews current concepts of risk evaluation and proposes standards for the critical appraisal of risk assessment methods. An adequate evaluation of a novel risk marker requires a sound research design, a representative at-risk population, and an adequate number of outcome events. Studies of a novel marker should report the degree to which it adds to the prognostic information provided by standard risk markers. No single statistical measure provides all the information needed to assess a novel marker, so measures of both discrimination and accuracy should be reported. The clinical value of a marker should be assessed by its effect on patient management and outcomes. In general, a novel risk marker should be evaluated in several phases, including initial proof of concept, prospective validation in independent populations, documentation of incremental information when added to standard risk markers, assessment of effects on patient management and outcomes, and ultimately, cost-effectiveness.

Abstract

Coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI) are alternative treatments for multivessel coronary disease. Although the procedures have been compared in several randomised trials, their long-term effects on mortality in key clinical subgroups are uncertain. We undertook a collaborative analysis of data from randomised trials to assess whether the effects of the procedures on mortality are modified by patient characteristics.We pooled individual patient data from ten randomised trials to compare the effectiveness of CABG with PCI according to patients' baseline clinical characteristics. We used stratified, random effects Cox proportional hazards models to test the effect on all-cause mortality of randomised treatment assignment and its interaction with clinical characteristics. All analyses were by intention to treat.Ten participating trials provided data on 7812 patients. PCI was done with balloon angioplasty in six trials and with bare-metal stents in four trials. Over a median follow-up of 5.9 years (IQR 5.0-10.0), 575 (15%) of 3889 patients assigned to CABG died compared with 628 (16%) of 3923 patients assigned to PCI (hazard ratio [HR] 0.91, 95% CI 0.82-1.02; p=0.12). In patients with diabetes (CABG, n=615; PCI, n=618), mortality was substantially lower in the CABG group than in the PCI group (HR 0.70, 0.56-0.87); however, mortality was similar between groups in patients without diabetes (HR 0.98, 0.86-1.12; p=0.014 for interaction). Patient age modified the effect of treatment on mortality, with hazard ratios of 1.25 (0.94-1.66) in patients younger than 55 years, 0.90 (0.75-1.09) in patients aged 55-64 years, and 0.82 (0.70-0.97) in patients 65 years and older (p=0.002 for interaction). Treatment effect was not modified by the number of diseased vessels or other baseline characteristics.Long-term mortality is similar after CABG and PCI in most patient subgroups with multivessel coronary artery disease, so choice of treatment should depend on patient preferences for other outcomes. CABG might be a better option for patients with diabetes and patients aged 65 years or older because we found mortality to be lower in these subgroups.

Abstract

Coronary atherosclerosis develops slowly over decades but is frequently characterized clinically by sudden unstable episodes. Patients who present with unstable coronary disease, such as acute myocardial infarction, may systematically differ from patients who present with relatively stable coronary disease, such as exertional angina.To examine whether medication use or patient characteristics influence the mode of initial clinical presentation of coronary disease.Case-control study.Large integrated health care delivery system in northern California.Adults whose first clinical presentation of coronary disease was either acute myocardial infarction (n = 916) or stable exertional angina (n = 468).Use of cardiac medications before the event from pharmacy databases and demographic, lifestyle, and clinical characteristics from self-report and clinical and administrative databases.Compared with patients with incident stable exertional angina, patients with incident acute myocardial infarction were more likely to be men, smokers, physically inactive, and hypertensive but were less likely to have a parental history of coronary disease. Patients presenting with myocardial infarction were much less likely to have received statins (19.3% vs. 40.4%; P < 0.001) and beta-blockers (19.0% vs. 47.7%; P < 0.001) than patients presenting with exertional angina. After adjustment for potential confounders, recent use of statins (adjusted odds ratio, 0.45 [95% CI, 0.32 to 0.62]) and beta-blockers (adjusted odds ratio, 0.26 [CI, 0.19 to 0.35]) was associated with lower likelihoods of presenting with an acute myocardial infarction than with stable angina.This observational study did not have information on all possible confounding factors, including use of aspirin therapy.Statin and beta-blocker use was associated with lower odds of presenting with an acute myocardial infarction than with stable angina. Additional studies are needed to confirm that these therapies protect against unstable, higher-risk clinical presentations of coronary disease.

Abstract

Eight randomized trials have evaluated whether the prophylactic use of an implantable cardioverter-defibrillator (ICD) improves survival among patients who are at risk for sudden death due to left ventricular systolic dysfunction but who have not had a life-threatening ventricular arrhythmia. We assessed the cost-effectiveness of the ICD in the populations represented in these primary-prevention trials.We developed a Markov model of the cost, quality of life, survival, and incremental cost-effectiveness of the prophylactic implantation of an ICD, as compared with control therapy, among patients with survival and mortality rates similar to those in each of the clinical trials. We modeled the efficacy of the ICD as a reduction in the relative risk of death on the basis of the hazard ratios reported in the individual clinical trials.Use of the ICD increased lifetime costs in every trial. Two trials--the Coronary Artery Bypass Graft (CABG) Patch Trial and the Defibrillator in Acute Myocardial Infarction Trial (DINAMIT)--found that the prophylactic implantation of an ICD did not reduce the risk of death and thus was both more expensive and less effective than control therapy. For the other six trials--the Multicenter Automatic Defibrillator Implantation Trial (MADIT) I, MADIT II, the Multicenter Unsustained Tachycardia Trial (MUSTT), the Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) trial, the Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) trial, and the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT)--the use of an ICD was projected to add between 1.01 and 2.99 quality-adjusted life-years (QALY) and between 68,300 dollars and 101,500 dollars in cost. Using base-case assumptions, we found that the cost-effectiveness of the ICD as compared with control therapy in these six populations ranged from 34,000 dollars to 70,200 dollars per QALY gained. Sensitivity analyses showed that this cost-effectiveness ratio would remain below 100,000 dollars per QALY as long as the ICD reduced mortality for seven or more years.Prophylactic implantation of an ICD has a cost-effectiveness ratio below 100,000 dollars per QALY gained in populations in which a significant device-related reduction in mortality has been demonstrated.

Abstract

Coronary bypass surgery (CABG) and angioplasty (PTCA) have been compared in several randomized trials, but data about long-term economic and quality-of-life outcomes are limited.Cost and quality-of-life data were collected prospectively from 934 patients who were randomized in the Bypass Angioplasty Revascularization Investigation (BARI) and followed up for 10 to 12 years. CABG had 53% higher costs initially, but the gap closed to <5% during the first 2 years; after 12 years, the mean cumulative cost of CABG patients was 123,000 dollars versus 120,750 dollars for PTCA, yielding a cost-effectiveness ratio of 14,300 dollars/life-year added. CABG patients experienced significantly greater improvement in their physical functioning for the first 3 years but not in later follow-up. Recurrent angina substantially reduced all quality-of-life measures throughout follow-up. Cumulative costs were significantly higher among patients with diabetes, heart failure, and comorbid conditions and among women; costs also were increased by angina, by the number of revascularization procedures, and among patients who died.Early differences between CABG and PTCA in costs and quality of life were no longer significant at 10 to 12 years of follow-up. CABG was cost-effective as compared with PTCA for multivessel disease.

Abstract

Use of coronary angiography after myocardial infarction has been controversial, with some physicians advocating routine use and others advocating selective use only after documentation of residual myocardial ischemia. The effects of these strategies on economic outcomes have not been established.We analyzed data from a randomized, controlled clinical trial conducted in 17 Department of Veterans Affairs hospitals that enrolled 876 clinically uncomplicated patients 24 to 72 hours after an acute non-Q-wave myocardial infarction. The routine invasive strategy included early coronary angiography with revascularization based on established guidelines. The conservative, ischemia-guided strategy included noninvasive testing with radionuclide ventriculography and exercise thallium scintigraphy, followed by coronary angiography in patients with objective evidence of myocardial ischemia. We measured the cost of hospitalization and outpatient visits and tests during follow-up and calculated the incremental cost-effectiveness ratio. The conservative, ischemia-guided strategy had lower costs than the routine invasive strategy, both during the initial hospitalization ($14 733 versus $19 256, P<0.001) and after a mean follow-up of 1.9 years ($39 707 versus $41 893, P=0.04). The hazard ratio for death was 0.72 (confidence limits, 0.51 to 1.01) in the conservative strategy. The conservative strategy had lower costs and better outcomes in 76% of 1000 bootstrap replications, and a cost-effectiveness ratio below $50 000 per year of life added in 96% of replications.A conservative, ischemia-guided strategy of selective coronary angiography and revascularization for patients who develop objective evidence of recurrent ischemia is more cost-effective than a strategy of routine coronary angiography after uncomplicated non-Q-wave myocardial infarction.

Abstract

Postmenopausal hormone therapy is commonly used by women for disease prevention, but its effects on quality of life have not been well documented.To determine the effect on quality of life of estrogen plus progestin therapy used as secondary prevention in women with coronary artery disease.A total of 2763 postmenopausal women with documented coronary artery disease (mean age, 67 years) in the Heart and Estrogen/Progestin Replacement Study, a randomized, placebo-controlled, double-blind trial conducted from January 1993 to July 1998 at outpatient and community settings at 20 US clinical centers.Participants were randomly assigned to receive either 0.625 mg/d of conjugated equine estrogen plus 2.5 mg/d of medroxyprogesterone acetate (n = 1380) or placebo (n = 1383) for 36 months.Physical activity, measured by the Duke Activity Status Index; energy/fatigue and mental health, measured by RAND scales; and depressive symptoms, measured on the Burnam screening scale, at 3 years of follow-up.In all patients, scores declined significantly over 3 years for physical function (-3.8; P

Abstract

Wide geographic variation in the use of coronary angiography after myocardial infarction has been documented internationally and within the United States. An associated variation in clinical outcomes has not been consistently demonstrated.We assessed the risk of death from heart disease and of any heart disease event (death, reinfarction, or rehospitalization) over a follow-up period of one to four years in 6851 patients hospitalized with acute myocardial infarction at 16 Kaiser Permanente hospitals from 1990 through 1992. The percentage of patients who underwent angiography within three months after infarction ranged from 30 to 77 percent. We selected a subcohort of 1109 patients from three hospitals with higher rates of angiography and four with lower rates for a record review to assess the severity of infarction, the number of coexisting conditions, treatments received, and the appropriateness and necessity of angiography, using established criteria.The rates of angiography were inversely related to the risk of death from heart disease (P= 0.03) and the risk of heart disease events (P<0.001) among the 16 hospitals after adjustment for age, sex, race, coexisting conditions, and the location of the infarction (subendocardial vs. transmural). In the subcohort, 440 patients met criteria indicating that angiography was necessary and 669 did not. Among the former, patients treated at hospitals with higher rates of angiography had a lower risk of death and of any heart disease event than those treated at hospitals with lower rates (hazard ratios, 0.67 and 0.72, respectively). Among the latter, the apparent benefits of being treated at hospitals with higher angiography rates were smaller (hazard ratios, 0.85 to 0.90 for death and any heart disease event, respectively).During the one to four years after myocardial infarction, patients treated at hospitals with higher rates of angiography had more favorable outcomes than those treated at hospitals with lower rates. This association was stronger among patients for whom published criteria indicated that angiography was necessary.

Abstract

It has been hypothesized that jobs that have both high psychological demands and low decision latitude ("job strain") can lead to coronary disease. The objective of this study was to test whether job strain was correlated with the presence of coronary disease at angiography or with long-term outcome in patients with angiographic coronary disease.Employed patients under the age of 65 years undergoing diagnostic coronary angiography completed a self-administered questionnaire about their job duties and work environment. Job strain was measured by the method of Karasek. Patients were separated into three groups, based on extent of coronary disease: significant disease (> or = 75% stenosis), insignificant disease (> 0% but < 75% stenosis), and normal coronary arteries. Statistical analyses were performed using logistic regression and the Cox proportional hazards model. The 1489 patients enrolled had a median age of 52 years; 76% were male and 88% were white. By design, all patients were employed, 60% in white-collar jobs and only 16% in jobs requiring heavy labor. Traditional cardiac risk factors were most prevalent in the 922 patients with significant coronary artery disease, at intermediate levels in the 204 patients with insignificant disease, and least prevalent in the 363 patients with normal coronary arteries (all P < .01). Job strain was actually more common in patients with normal coronary arteries (35%) than in patients with insignificant (26%) or significant disease (25%, P < .002). In a multivariate analysis, job strain was not significantly correlated with the presence of coronary disease. Job strain was not correlated with angina frequency at the time of angiography. Job strain was not a predictor of cardiac events (cardiac death or nonfatal myocardial infarction) during follow-up.Job strain was not correlated with the prevalence or severity of coronary artery disease in a cohort of patients undergoing coronary angiography. The outcome of patients with angiographically defined coronary disease was not affected by the level of job strain as measured by the method of Karasek.

Abstract

To determine whether preoperative coronary angiography and revascularization improve short-term outcomes in patients undergoing noncardiac vascular surgery.Decision analysis.Patients undergoing elective vascular surgery who had either no angina or mild angina and a positive dipyridamole-thallium scan result.Three strategies were compared. The first strategy was to proceed directly to vascular surgery. The second was to perform coronary angiography, followed by selective coronary revascularization, before proceeding to vascular surgery and to cancel vascular surgery in patients with severe inoperable coronary artery disease (CAD). The third was to perform coronary angiography, followed by selective coronary revascularization, before proceeding to vascular surgery and to perform vascular surgery in patients with inoperable CAD.Mortality, nonfatal myocardial infarction, stroke, uncorrected vascular disease, and cost. All outcomes were assessed within 3 months.Proceeding directly to vascular surgery led to lower morbidity and cost in the base case analysis. The coronary angiography strategy led to higher mortality if vascular surgery would proceed in patients with inoperable CAD, but led to slightly lower mortality if vascular surgery were canceled in patients with inoperable CAD. The coronary angiography strategy also led to lower mortality when vascular surgery was particularly risky.Decision analysis indicates vascular surgery without preoperative coronary angiography generally leads to better outcomes. Preoperative coronary angiography should be reserved for patients whose estimated mortality from vascular surgery is substantially higher than average.

Abstract

Much attention has been directed to the use of medical resources and to patients' outcomes in Canada as compared with the United States. We compared U.S. and Canadian patients with respect to their use of medical resources and their quality of life during the year after acute myocardial infarction.A total of 2600 U.S. and 400 Canadian patients were randomly selected from the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) trial. Base-line data from their initial hospitalizations were analyzed, and the patients were then interviewed by telephone 30 days, 6 months, and 1 year after myocardial infarction to determine their use of medical care and quality of life.The Canadian patients typically stayed in the hospital one day longer (P = 0.009) than the U.S. patients but had a much lower rate of cardiac catheterization (25 percent vs. 72 percent, P < 0.001), coronary angioplasty (11 percent vs. 29 percent, P < 0.001), and coronary bypass surgery (3 percent vs. 14 percent, P < 0.001). At one year 24 percent of the Canadian and 53 percent of the U.S. patients had undergone angioplasty or bypass surgery at least once (P < 0.001). The Canadian had more visits to physicians during the follow-up year (P < 0.001), but fewer visits to specialists (P < 0.001). At 30 days, functional status was equivalent in the patients from the two countries. However, after one year the U.S. patients had substantially more improvement than the Canadian patients (P < 0.001). The prevalence of chest pain and dyspnea at one year was higher among the Canadian patients (34 percent vs. 21 percent and 45 percent vs. 29 percent, respectively; P < 0.001).The Canadian patients had more cardiac symptoms and worse functional status one year after acute myocardial infarction than the U.S. patients. The Canadian patients also underwent fewer invasive cardiac procedures and had fewer visits to specialist physicians. These results suggest, but do not prove, that the more aggressive pattern of care in the United States may have been responsible for the better quality of life.

Abstract

To develop a brief, self-administered questionnaire that accurately measures functional capacity and assesses aspects of quality of life, 50 subjects undergoing exercise testing with measurement of peak oxygen uptake were studied. All subjects were questioned about their ability to perform a variety of common activities by an interviewer blinded to exercise test findings. A 12-item scale (the Duke Activity Status Index) was then developed that correlated well with peak oxygen uptake (Spearman correlation coefficient 0.80). To test this new index, an independent group of 50 subjects completed a self-administered questionnaire to determine functional capacity and underwent exercise testing with measurement of peak oxygen uptake. The Duke Activity Status Index correlated significantly (p less than 0.0001) with peak oxygen uptake (Spearman correlation coefficient 0.58) in this independent sample. The Duke Activity Status Index is a valid measure of functional capacity that can be obtained by self-administered questionnaire.

Abstract

Clinical decisions are most secure when based on findings from several large randomized clinical trials, but relevant randomized trial data are often unavailable. Analyses using clinical data bases might provide useful information if statistical methods can adequately correct for the lack of randomization. To test this approach, the findings of the three major randomized trials of coronary bypass surgery were compared with predictions of multivariable statistical models derived from observations in the Duke Cardiovascular Disease Databank. Clinical characteristics of patients at Duke University Medical Center who met eligibility requirements for each major randomized trial were used in the models to predict 5 year survival rates expected for medical and surgical therapy in each randomized trial. Model predictions agreed well with randomized trial results and were within the 95% confidence limits of the observed survival rates in 24 (92%) of 26 clinical subgroups. The overall correlation between predicted and observed survival rates was good (Spearman coefficient 0.73, p less than 0.0001). These results suggest that carefully performed analyses of observational data can complement the results of randomized trials.

Abstract

Unlike the predictive value of a diagnostic test, which depends on the prevalence of disease in the population tested, its sensitivity and specificity have been assumed to be constants. This assumption was examined in patients who had both exercise electrocardiography and cardiac catheterization. The effects on sensitivity of factors from clinical history, catheterization, and exercise performance were defined by multivariable logistic regression analysis in 1,401 patients with coronary disease; effects on specificity were defined by a similar analysis in 868 patients without coronary disease. Five factors had significant, independent effects on exercise electrocardiographic sensitivity: maximal exercise heart rate, number of diseased coronary arteries, type of angina, and the patient's age and sex. Only maximal exercise heart rate had a significant, independent effect on exercise electrocardiographic specificity. Thus, the sensitivity and specificity of exercise electrocardiography vary with clinical history, extent of disease, and treadmill performance; the sensitivity and specificity of other diagnostic tests may also vary.

Abstract

First-time syncopal episodes usually occur in adults of working age, but their impact on occupational safety and employment remains unknown. We examined the associations of syncope with occupational accidents and termination of employment.Through linkage of Danish population-based registers, we included all residents 18 to 64 years from 2008 to 2012. Among 3 410 148 eligible individuals, 21 729 with a first-time diagnosis of syncope were identified, with a median age 48.4 years (first to third quartiles, 33.0-59.5), and 10 757 (49.5%) employed at time of the syncope event. Over a median follow-up of 3.2 years (first to third quartiles, 2.0-4.5), 622 people with syncope had an occupational accident requiring hospitalization (2.1/100 person-years). In multiple Poisson regression analysis, the incidence rate ratio in the employed syncope population was higher than in the employed general population (1.44; 95% confidence interval [CI], 1.33-1.55) and more pronounced in people with recurrences (2.02; 95% CI, 1.47-2.78). The 2-year risk of termination of employment was 31.3% (95% CI, 30.4%-32.3%), which was twice the risk of the reference population (15.2%; 95% CI, 14.7%-15.7%), using the Aalen-Johansen estimator. Factors associated with termination of employment were age <40 years (incidence rate ratio, 1.48; 95% CI, 1.37-1.59), cardiovascular disease (1.20; 95% CI, 1.06-1.36), depression (1.72; 95% CI, 1.55-1.90), and low educational level (2.61; 95% CI, 2.34-2.91).In this nationwide cohort, syncope was associated with a 1.4-fold higher risk of occupational accidents and a 2-fold higher risk of termination of employment compared with the employed general population.

Abstract

This study assessed the cost-effectiveness of left ventricular assist devices (LVADs) as destination therapy in ambulatory patients with advanced heart failure.LVADs improve survival and quality of life in inotrope-dependent heart failure, but data are limited as to their value in less severely ill patients.We determined costs of care among Medicare beneficiaries before and after LVAD implantation from 2009 to 2010. We used these costs and efficacy data from published studies in a Markov model to project the incremental cost-effectiveness ratio (ICER) of destination LVAD therapy compared with that of medical management. We discounted costs and benefits at 3% annually and report costs as 2016 U.S. dollars.The mean cost of LVAD implantation was $175,420. The mean cost of readmission was lower before LVAD than after ($12,377 vs. $19,465, respectively; p < 0.001), while monthly outpatient costs were similar ($3,364 vs. $2,974, respectively; p = 0.54). In the lifetime simulation model, LVAD increased quality-adjusted life-years (QALYs) (4.41 vs. 2.67, respectively), readmissions (13.03 vs. 6.35, respectively), and costs ($726,200 vs. $361,800, respectively) compared with medical management, yielding an ICER of $209,400 per QALY gained and $597,400 per life-year gained. These results were sensitive to LVAD readmission rates and outpatient care costs; the ICER would be $86,900 if these parameters were 50% lower.LVADs in non-inotrope-dependent heart failure patients improved quality of life but substantially increased lifetime costs because of frequent readmissions and costly follow-up care. LVADs may provide good value if outpatient costs and adverse events can be reduced.

Abstract

To study the contemporary, real-world clinical and economic burden associated with angina after percutaneous coronary intervention (PCI).Angina adversely affects quality of life and medical costs, yet data on real-world prevalence of angina following PCI and its associated economic consequences are limited.In a multi-payer administrative claims database, we identified adults with incident inpatient PCI admissions between 2008 and 2011 who had at least 12 months of continuous medical and pharmacy benefits before and after the procedure. Patients were followed for up to 36 months. Using claims, we ascertained post-PCI outcomes: angina or chest pain, acute myocardial infarction, acute coronary syndrome, repeat PCI, healthcare service utilization, and costs.Among 51,710 study patients (mean age 61.8, 72% male), post-PCI angina or chest pain was present in 28% by 12 months and 40% by 36 months. Compared with patients who did not experience chest pain, angina or ACS, total healthcare costs in the first year after the index PCI were 1.8 times greater for patients with angina or chest pain ($32,437 vs. $17,913, P

Abstract

Higher body mass index (BMI) is an important risk factor for atrial fibrillation (AF). The adipokines leptin, adiponectin and resistin are correlates of BMI, but their association with incident AF is not well known. We explored this relationship in a large cohort of postmenopausal women.We studied an ethnically diverse cohort of community-dwelling postmenopausal women aged 50-79 who were nationally recruited at 40 clinical centres as part of the Women's Health Initiative investigation. Participants underwent measurements of baseline serum leptin, adiponectin and resistin levels and were followed for incident AF. Adipokine levels were log transformed and normalised using inverse probability weighting. Cox proportional hazard regression models were used to estimate associations with adjustment for known AF risk factors.Of the 4937 participants included, 892 developed AF over a follow-up of 11.1 years. Those with AF had higher mean leptin (14.9 pg/mL vs 13.9 pg/mL), adiponectin (26.3 ug/mL vs 24.5 ug/mL) and resistin (12.9 ng/mL vs 12.1 ng/mL) levels. After multivariable adjustment, neither log leptin nor log adiponectin levels were significantly associated with incident AF. However, log resistin levels remained significantly associated with incident AF (HR=1.57 per 1 log (ng/mL) increase, p=0.006). Additional adjustment for inflammatory cytokines only partially attenuated the association between resistin and incident AF (HR=1.43, p=0.06 adjusting for C-reactive protein (CRP); HR=1.39, p=0.08 adjusting for IL-6). Adjusting for resistin partially attenuated the association between BMI and incident AF (HR=1.14 per 5 kg/m(2), p=0.006 without resistin; HR=1.12, p=0.02 with resistin).In women, elevated levels of serum resistin are significantly associated with higher rates of incident AF and partially mediate the association between BMI and AF. In the same population, leptin and adiponectin levels are not significantly associated with AF.

Abstract

Since the 1980s, when the American College of Cardiology (ACC) and the American Heart Association (AHA) established a joint task force to examine the use of cardiovascular procedures and therapies, cardiologists have been leaders in the development of clinical practice guidelines. The ACC/AHA guidelines development process has evolved considerably over the last 30 or more years. Guidelines now focus on clinical conditions, such as angina, instead of procedures, such as bypass surgery. There is a formal organizational structure, with dedicated staff, a standing committee on practice guidelines, and specific panels of volunteer experts on each topic. This process tightly manages conflicts of interest and strives for evidence-based, as opposed to opinion-based, guidelines, with a clear citation of the supporting evidence. Traditional clinical guidelines consider only what is best for the individual patient, and have explicitly not considered the cost to society. Nevertheless, in many guidelines development meetings, high cost was implicitly considered: if a procedure was extremely costly, the evidence needed to be very strong. The Guidelines Committee recognized that cost considerations ought to be made more transparent, and that the evidence on economic value should be explicitly cited when available. These considerations were formalized by a recent white paper on incorporating economic considerations into ACC/AHA guidelines. In considering value, it is necessary to assess the quality of the evidence as well as to define levels of value. The next ACC/AHA guideline will incorporate value as a part of its recommendations. This will be an evidence-based process in which published economic assessments relating to key questions will be reviewed.

Abstract

The incidence of atrial fibrillation (AF) is higher in non-Hispanic whites (NHWs) compared with other race-ethnic groups, despite more favorable cardiovascular risk profiles. To explore reasons for this paradox, we compared the hazards of AF from traditional and other risk factors between 4 race-ethnic groups in a large cohort of postmenopausal women.We included 114,083 NHWs, 11,876 African Americans, 5,174 Hispanics, and 3,803 Asians from the Women's Health Initiative free of AF at baseline. Women, averaging 63 years old, were followed up for incident AF using hospitalization records and diagnostic codes from Medicare claims.Over a mean of 13.7 years, 19,712 incident cases of AF were recorded. Despite a higher burden of hypertension, diabetes, and obesity, annual AF incidence was lower among nonwhites (0.7%, 0.4%, and 0.4% for African American, Hispanic, and Asian participants, respectively, compared with 1.2% for NHWs). The hazards of AF from hypertension, diabetes, obesity, heart failure, and coronary artery disease were similar across race-ethnic groups. Major risk factors, including hypertension, obesity, diabetes, smoking, peripheral arterial disease, coronary artery disease, and heart failure, accounted for an attributable risk of 50.3% in NHWs, 83.1% in African Americans, 65.6% in Hispanics, and 37.4% in Asians. Established AF prediction models performed comparably across race-ethnic groups.In this large study of postmenopausal women, traditional cardiovascular risk factors conferred a similar degree of individual risk of AF among 4 race-ethnic groups. However, major AF risk factors conferred a higher-attributable risk in African Americans and Hispanics compared with NHWs and Asians.

Abstract

Randomized trials of left atrial appendage (LAA) closure with the Watchman device have shown varying results, and its cost effectiveness compared with anticoagulation has not been evaluated using all available contemporary trial data.We used a Markov decision model to estimate lifetime quality-adjusted survival, costs, and cost effectiveness of LAA closure with Watchman, compared directly with warfarin and indirectly with dabigatran, using data from the long-term (mean 3.8 year) follow-up of Percutaneous Closure of the Left Atrial Appendage Versus Warfarin Therapy for Prevention of Stroke in Patients With Atrial Fibrillation (PROTECT AF) and Prospective Randomized Evaluation of the Watchman LAA Closure Device in Patients With Atrial Fibrillation (PREVAIL) randomized trials. Using data from PROTECT AF, the incremental cost-effectiveness ratios compared with warfarin and dabigatran were $20 486 and $23 422 per quality-adjusted life year, respectively. Using data from PREVAIL, LAA closure was dominated by warfarin and dabigatran, meaning that it was less effective (8.44, 8.54, and 8.59 quality-adjusted life years, respectively) and more costly. At a willingness-to-pay threshold of $50 000 per quality-adjusted life year, LAA closure was cost effective 90% and 9% of the time under PROTECT AF and PREVAIL assumptions, respectively. These results were sensitive to the rates of ischemic stroke and intracranial hemorrhage for LAA closure and medical anticoagulation.Using data from the PROTECT AF trial, LAA closure with the Watchman device was cost effective; using PREVAIL trial data, Watchman was more costly and less effective than warfarin and dabigatran. PROTECT AF enrolled more patients and has substantially longer follow-up time, allowing greater statistical certainty with the cost-effectiveness results. However, longer-term trial results and postmarketing surveillance of major adverse events will be vital to determining the value of the Watchman in clinical practice.

Abstract

High body mass index (BMI) is a risk factor for atrial fibrillation (AF). The aim of this study was to determine whether lean body mass (LBM) predicts AF.The Women's Health Initiative is a study of post-menopausal women aged 50-79 enrolled at 40 US centres from 1994 to 1998. A subset of 11 393 participants at three centres underwent dual-energy X-ray absorptiometry. Baseline demographics and clinical histories were recorded. Incident AF was identified using hospitalization records and diagnostic codes from Medicare claims. A multivariable Cox hazard regression model adjusted for demographic and clinical risk factors was used to evaluate associations between components of body composition and AF risk. After exclusion for prevalent AF or incomplete data, 8832 participants with an average age of 63.3 years remained for analysis. Over the 11.6 years of average follow-up time, 1035 women developed incident AF. After covariate adjustment, all measures of LBM were independently associated with higher rates of AF: total LBM [hazard ratio (HR) 1.24 per 5 kg increase, 95% confidence intervals (CI) 1.14-1.34], central LBM (HR 1.51 per 5 kg increase, 95% CI 1.31-1.74), and peripheral LBM (HR 1.39 per 5 kg increase, 95% CI 1.19-1.63). The association between total LBM and AF remained significant after adjustment for total fat mass (HR 1.22 per 5 kg increase, 95% CI 1.13-1.31).Greater LBM is a strong independent risk factor for AF. After adjusting for obesity-related risk factors, the risk of AF conferred by higher BMI is primarily driven by the association between LBM and AF.

Abstract

Composite endpoints are commonly used as the primary measure of efficacy in heart failure clinical trials to assess the overall treatment effect and to increase the efficiency of trials. Clinical trials still must enrol large numbers of patients to accrue a sufficient number of outcome events and have adequate power to draw conclusions about the efficacy and safety of new treatments for heart failure. Additionally, the societal and health system perspectives on heart failure have raised interest in ascertaining the effects of therapy on outcomes such as repeat hospitalization and the patient's burden of disease. Thus, novel methods for using composite endpoints in clinical trials (e.g. clinical status composite endpoints, recurrent event analyses) are being applied in current and planned trials. Endpoints that measure functional status or reflect the patient experience are important but used cautiously because heart failure treatments may improve function yet have adverse effects on mortality. This paper discusses the use of traditional and new composite endpoints, identifies qualities of robust composites, and outlines opportunities for future research.

Abstract

Syncope may have serious consequences for traffic safety. Current clinical guideline recommendations on driving following syncope are primarily based on expert consensus.To identify whether there is excess risk of motor vehicle crashes among patients with syncope compared with the general population.Danish nationwide cohort study from January 1, 2008, to December 31, 2012. Through individual-level linkage of nationwide administrative registers, all Danish residents 18 years or older were identified. Of 4 265 301 eligible Danish residents, we identified 41 039 individuals with a first-time diagnosis of syncope from emergency department or hospital.Rate of motor vehicle crashes (including nonfatal and fatal crashes), based on multivariate Poisson regression models, using the total Danish population as reference.The 41 039 patients with syncope had a median age of 66 years (interquartile range [IQR], 47-78 years); 51.0% were women; and 34.8% had cardiovascular disease. Through a median follow-up of 2.0 years (IQR, 0.8-3.3 years), 1791 patients with syncope (4.4%) had a motor vehicle crash, 78.1% of which led to injury (n = 1398) and 0.3% to death (n = 6). The crude incidence rate of motor vehicle crashes was almost doubled among patients with syncope (20.6 per 1000 person-years; 95% CI, 19.7-21.6) compared with the general population (12.1; 95% CI, 12.0-12.1), with a rate ratio (RR) of 1.83 (95% CI, 1.74-1.91) after adjustment for age, sex, socioeconomic position, and relevant comorbidities and pharmacotherapy. Men had a relatively higher rate of motor vehicle crashes (RR, 1.91; 95% CI, 1.79-2.03) than women (RR, 1.74; 95% CI, 1.63-1.87). The excess risk of motor vehicle crashes persisted throughout the follow-up period. The 5-year crash risk following syncope was 8.2% (95% CI, 7.5%-8.8%) among the population aged 18 to 69 years compared with 5.1% (95% CI, 4.7%-5.4%) in the general population.Prior hospitalization for syncope was associated with increased risk of motor vehicle crashes throughout the follow-up period. This study suggests that syncope should be considered as one of several factors in a broad assessment of fitness to drive.

Abstract

-Recent genome wide association studies (GWAS) have identified 49 single nucleotide polymorphisms (SNPs) associated with clinical CAD. The mechanism by which these loci influence risk remains largely unclear.-We examined the association between a genetic risk score (GRS) composed of high-risk alleles at the 49 SNPs and the degree of subclinical coronary atherosclerosis in 7,798 participants from six studies stratified into four age groups at the time of assessment (15-34, 35-54, 55-74, >75 years). Atherosclerosis was quantified by staining and direct visual inspection of the right coronary artery in the youngest group, and by scanning for coronary artery calcification in the remaining groups. We defined cases as subjects within the top quartile of degree of atherosclerosis in three groups and as subjects with a CAC>0 in the fourth (35-54 years) where less than one quarter had any CAC. In our meta-analysis of all strata, we found one SD increase in the GRS increased the risk of advanced subclinical coronary atherosclerosis by 36% (p=8.3×10(-25)). This increase in risk was significant in all four age groups including the youngest group where atherosclerosis consisted primarily of raised lesions without macroscopic evidence of plaque rupture or thrombosis. Results were similar when we restricted the GRS to 32 SNPs not associated with traditional risk factors (TRFs) and/or when we adjusted for TRFs.-A GRS for clinical CAD is associated with advanced subclinical coronary atherosclerosis throughout the life-course. This association is apparent even at the earliest, uncomplicated stages of atherosclerosis.

Abstract

Cardiac resynchronization therapy (CRT) reduces mortality and heart failure hospitalizations in patients with mild heart failure.To estimate the cost-effectiveness of adding CRT to an implantable cardioverter-defibrillator (CRT-D) compared with implantable cardioverter-defibrillator (ICD) alone among patients with left ventricular systolic dysfunction, prolonged intraventricular conduction, and mild heart failure.Markov decision model.Clinical trials, clinical registries, claims data from Centers for Medicare & Medicaid Services, and Centers for Disease Control and Prevention life tables.Patients aged 65 years or older with a left ventricular ejection fraction (LVEF) of 30% or less, QRS duration of 120 milliseconds or more, and New York Heart Association (NYHA) class I or II symptoms.Lifetime.Societal.CRT-D or ICD alone.Life-years, quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs).Use of CRT-D increased life expectancy (9.8 years versus 8.8 years), QALYs (8.6 years versus 7.6 years), and costs ($286 500 versus $228 600), yielding a cost per QALY gained of $61 700.The cost-effectiveness of CRT-D was most dependent on the degree of mortality reduction: When the risk ratio for death was 0.95, the ICER increased to $119 600 per QALY. More expensive CRT-D devices, shorter CRT-D battery life, and older age also made the cost-effectiveness of CRT-D less favorable.The estimated mortality reduction for CRT-D was largely based on a single trial. Data on patients with NYHA class I symptoms were limited. The cost-effectiveness of CRT-D in patients with NYHA class I symptoms remains uncertain.In patients with an LVEF of 30% or less, QRS duration of 120 milliseconds or more, and NYHA class II symptoms, CRT-D appears to be economically attractive relative to ICD alone when a reduction in mortality is expected.National Institutes of Health, University of Copenhagen, U.S. Department of Veterans Affairs.

Abstract

To characterize the association of antiretroviral drug combinations on risk of cardiovascular events. Certain antiretroviral medications for human immunodeficiency virus (HIV) have been implicated in increasing risk of cardiovascular disease. However, antiretroviral drugs are typically prescribed in combination. We characterized the association of current exposure to antiretroviral drug combinations on risk of cardiovascular events including myocardial infarction, stroke, percutaneous coronary intervention, and coronary artery bypass surgery. We used the Veterans Health Administration Clinical Case Registry to analyze data from 24 510 patients infected with HIV from January 1996 through December 2009. We assessed the association of current exposure to 15 antiretroviral drugs and 23 prespecified combinations of agents on the risk of cardiovascular event by using marginal structural models and Cox models extended to accommodate time-dependent variables. Over 164 059 person-years of follow-up, 934 patients had a cardiovascular event. Current exposure to abacavir, efavirenz, lamivudine, and zidovudine was significantly associated with increased risk of cardiovascular event, with odds ratios ranging from 1.40 to 1.53. Five combinations were significantly associated with increased risk of cardiovascular event, all of which involved lamivudine. One of these-efavirenz, lamivudine, and zidovudine-was the second most commonly used combination and was associated with a risk of cardiovascular event that is 1.60 times that of patients not currently exposed to the combination (odds ratio = 1.60, 95% confidence interval, 1.25-2.04). In the VA cohort, exposure to both individual drugs and drug combinations was associated with modestly increased risk of a cardiovascular event.

Abstract

Platelet inhibition after percutaneous coronary intervention (PCI) reduces the risk of myocardial infarction (MI) but increases the risk of bleeding. MIs and bleeds during the index hospitalization for PCI are known to negatively affect long-term outcomes. The impact of spontaneous bleeding occurring after discharge on long-term mortality is unknown.This study sought to examine, in a real-world cohort, the association between spontaneous major bleeding or MI after PCI and long-term mortality.We conducted a retrospective cohort study of patients ≥30 years of age who underwent a PCI between 1996 and 2008 in an integrated healthcare delivery system. We used extended Cox regression to examine the associations of spontaneous bleeding and MI with all-cause mortality, after adjustment for time-updated demographics, comorbidities, periprocedural events, and longitudinal medication exposure.Among 32,906 patients who had a PCI and survived the index hospitalization, 530 had bleeds and 991 had MIs between 7 and 365 days post-discharge. There were 4,048 deaths over a mean follow-up of 4.42 years. The crude annual death rate after a spontaneous bleed (9.5%) or MI (7.6%) was higher than among patients who experienced neither event (2.6%). Bleeding was associated with an increased rate of death (adjusted hazard ratio [HR]: 1.61, 95% confidence interval [CI]: 1.30 to 2.00), similar to that after an MI (HR: 1.91; 95% CI: 1.62 to 2.25). The association of bleeding with death remained significant after additional adjustment for the longitudinal use of antiplatelet agents.Spontaneous bleeding after a PCI was independently associated with higher long-term mortality, and conveyed a risk comparable to that of an MI during follow-up. This tradeoff between efficacy and safety bolsters the argument for personalizing antiplatelet therapy after PCI on the basis of the patient's long-term risk of both thrombotic and bleeding events.

Abstract

ASCERT (American College of Cardiology Foundation and the Society of Thoracic Surgeons Collaboration on the Comparative Effectiveness of Revascularization Strategies) was a large observational study designed to compare the long-term effectiveness of coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI) to treat coronary artery disease (CAD) over 4 to 5 years.This study examined the cost-effectiveness of CABG versus PCI for stable ischemic heart disease.The Society of Thoracic Surgeons and American College of Cardiology Foundation databases were linked to the Centers for Medicare and Medicaid Services claims data. Costs for the index and observation period (2004 to 2008) hospitalizations were assessed by diagnosis-related group Medicare reimbursement rates; costs beyond the observation period were estimated from average Medicare participant per capita expenditure. Effectiveness was measured via mortality and life-expectancy data. Cost and effectiveness comparisons were adjusted using propensity score matching with the incremental cost-effectiveness ratio expressed as cost per quality-adjusted life-year gained.CABG patients (n = 86,244) and PCI patients (n = 103,549) were at least 65 years old with 2- or 3-vessel coronary artery disease. Adjusted costs were higher for CABG for the index hospitalization, study period, and lifetime by $10,670, $8,145, and $11,575, respectively. Patients undergoing CABG gained an adjusted average of 0.2525 and 0.3801 life-years relative to PCI over the observation period and lifetime, respectively. The life-time incremental cost-effectiveness ratio of CABG compared to PCI was $30,454/QALY gained.Over a period of 4 years or longer, patients undergoing CABG had better outcomes but at higher costs than those undergoing PCI.

Abstract

Drug-eluting stents (DES) have largely replaced bare-metal stents (BMS) for percutaneous coronary intervention (PCI). It is uncertain, however, whether introduction of DES had a significant impact on the comparative effectiveness of PCI versus coronary artery bypass graft surgery (CABG) for death and myocardial infarction (MI).We identified Medicare beneficiaries aged ≥66 years who underwent multivessel CABG or multivessel PCI and matched PCI and CABG patients on propensity score. We defined the BMS era as January 1999 to April 2003 and the DES era as May 2003 to December 2006. We compared 5-year outcomes of CABG and PCI using Cox proportional hazards models, adjusting for baseline characteristics and year of procedure and tested for a statistically significant interaction (P(int)) of DES era with treatment (CABG or PCI).Five-year survival improved from the BMS era to the DES era by 1.2% for PCI and by 1.1% for CABG, and the CABG:PCI hazard ratio was unchanged (0.90 vs 0.90; P(int) = .96). Five-year MI-free survival improved by 1.4% for PCI and 1.1% for CABG, with no change in the CABG:PCI hazard ratio (0.81 vs 0.82; P(int) = .63). By contrast, survival-free of MI or repeat coronary revascularization improved from the BMS era to the DES era by 5.7% for PCI and 0.9% for CABG, and the CABG:PCI hazard ratio changed significantly (0.50 vs 0.57, P(int) ≤ .0001).The introduction of DES did not alter the comparative effectiveness of CABG and PCI with respect to hard cardiac outcomes.

Abstract

The revised cardiac risk index (RCRI) holds a central role in preoperative cardiac risk stratification in noncardiac surgery. Its performance in unselected populations, including different age groups, has, however, not been systematically investigated. We assessed the relationship of RCRI with major adverse cardiovascular events in an unselected cohort of patients undergoing elective, noncardiac surgery overall and in different age groups.We followed up all individuals ≥ 25 years who underwent major elective noncardiac surgery in Denmark (January 1, 2005, to November 30, 2011) for the 30-day risk of major adverse cardiovascular events (ischemic stroke, myocardial infarction, or cardiovascular death). There were 742 of 357,396 (0.2%), 755 of 74.889 (1.0%), 521 of 11,921 (4%), and 257 of 3146 (8%) major adverse cardiovascular events occurring in RCRI classes I, II, III, and IV. Multivariable odds ratio estimates were as follows: ischemic heart disease 3.30 (95% confidence interval, 2.96-3.69), high-risk surgery 2.70 (2.46-2.96), congestive heart failure 2.65 (2.29-3.06), cerebrovascular disease 10.02 (9.08-11.05), insulin therapy 1.62 (1.37-1.93), and kidney disease 1.45 (1.33-1.59). Modeling RCRI classes as a continuous variable, C statistic was highest among age group 56 to 65 years (0.772) and lowest for those aged >85 years (0.683). Sensitivity of RCRI class >I (ie, having ≥ 1 risk factor) for capturing major adverse cardiovascular events was 59%, 71%, 64%, 66%, and 67% in patients aged ≤ 55, 56 to 65, 66 to 75, 76 to 85, and >85 years, respectively; the negative predictive values were >98% across all age groups.In a nationwide unselected cohort, the performance of the RCRI was similar to that of the original cohort. Having ≥ 1 risk factor was of moderate sensitivity, but high negative predictive value for all ages.

Abstract

Heart failure is an established risk factor for poor outcomes in patients undergoing non-cardiac surgery, yet risk stratification remains a clinical challenge. We developed an index for 30-day mortality risk prediction in this particular group.All individuals with heart failure undergoing non-cardiac surgery between October 23 2004 and October 31 2011 were included from Danish administrative registers (n = 16 827). In total, 1787 (10.6%) died within 30 days. In a simple risk score based on the variables from the revised cardiac risk index, plus age, gender, acute surgery, and body mass index category the following variables predicted mortality (points): male gender (1), age 56-65 years (2), age 66-75 years (4), age 76-85 years (5), or age >85 years (7), being underweight (4), normal weight (3), or overweight (1), undergoing acute surgery (5), undergoing high-risk procedures (intra-thoracic, intra-abdominal, or suprainguinal aortic) (3), having renal disease (1), cerebrovascular disease (1), and use of insulin (1). The c-statistic was 0.79 and calibration was good. Mortality risk ranged from <2% for a score <5 to >50% for a score ≥20. Internal validation by bootstrapping (1000 re-samples) provided c-statistic of 0.79. A more complex risk score based on stepwise logistic regression including 24 variables at P

Abstract

Acute kidney injury (AKI) is a known complication after coronary revascularization, but few studies have directly compared the incidence of AKI after coronary artery bypass surgery (CABG) or after percutaneous coronary intervention (PCI) in similar patients.The aim of this study was to investigate whether multivessel CABG compared with PCI as an initial revascularization strategy is associated with a higher risk for AKI.A retrospective analysis of patients undergoing first documented coronary revascularization was conducted using 2 complementary cohorts: 1) Kaiser Permanente Northern California, a diverse, integrated health care delivery system; and 2) Medicare beneficiaries, a large, nationally representative older cohort. AKI was defined in the Kaiser Permanente Northern California cohort by an increase in serum creatinine of ≥0.3 mg/dl or ≥150% above baseline and in the Medicare cohort by discharge diagnosis codes and the use of dialysis.The incidence of AKI was 20.4% in the Kaiser Permanente Northern California cohort and 6.2% in the Medicare cohort. The incidence of AKI requiring dialysis was <1%. CABG was associated with a 2- to 3-fold significantly higher adjusted odds for developing AKI compared with PCI in both cohorts.AKI is common after multivessel coronary revascularization and is more likely after CABG than after PCI. The risk for AKI should be considered when choosing a coronary revascularization strategy, and ways to prevent AKI after coronary revascularization are needed.

Abstract

Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with increased risk of stroke and death. Obesity is an independent risk factor for AF, but modifiers of this risk are not well known. We studied the roles of obesity, physical activity, and their interaction in conferring risk of incident AF.The Women's Health Initiative (WHI) Observational Study was a prospective observational study of 93 676 postmenopausal women followed for an average of 11.5 years. Incident AF was identified using WHI-ascertained hospitalization records and diagnostic codes from Medicare claims. A multivariate Cox's hazard regression model adjusted for demographic and clinical risk factors was used to evaluate the interaction between obesity and physical activity and its association with incident AF. After exclusion of women with prevalent AF, incomplete data, or underweight body mass index (BMI), 9792 of the remaining 81 317 women developed AF. Women were, on average, 63.4 years old, 7.8% were African American, and 3.6% were Hispanic. Increased BMI (hazard ratio [HR], 1.12 per 5-kg/m(2) increase; 95% confidence interval [CI], 1.10 to 1.14) and reduced physical activity (>9 vs. 0 metabolic equivalent task hours per week; HR, 0.90; 95% CI, 0.85 to 0.96) were independently associated with higher rates of AF after multivariate adjustment. Higher levels of physical activity reduced the AF risk conferred by obesity (interaction P=0.033).Greater physical activity is associated with lower rates of incident AF and modifies the association between obesity and incident AF.

Abstract

The effectiveness of beta-blockers for preventing cardiac events has been questioned for patients who have coronary heart disease (CHD) without a prior myocardial infarction (MI).The purpose of this study was to assess the association of beta-blockers with outcomes among patients with new-onset CHD.We studied consecutive patients discharged after the first CHD event (acute coronary syndrome or coronary revascularization) between 2000 and 2008 in an integrated healthcare delivery system who did not use beta-blockers in the year before entry. We used time-varying Cox regression models to determine the hazard ratio (HR) associated with beta-blocker treatment and used treatment-by-covariate interaction tests (pint) to determine whether the association differed for patients with or without a recent MI.A total of 26,793 patients were included, 19,843 of whom initiated beta-blocker treatment within 7 days of discharge from their initial CHD event. Over an average of 3.7 years of follow-up, 6,968 patients had an MI or died. Use of beta-blockers was associated with an adjusted HR for mortality of 0.90 (95% confidence limits [CL]: 0.84 to 0.96), and an adjusted HR for death or MI of 0.92 (CL: 0.87 to 0.97). The association between beta-blockers and outcomes differed significantly between patients with and without a recent MI (HR for death: 0.85 vs. 1.02, pint = 0.007; and HR for death or MI: 0.87 vs. 1.03, pint = 0.005).Use of beta-blockers among patients with new-onset CHD was associated with a lower risk of cardiac events only among patients with a recent MI.

Abstract

Capturing long-term outcomes from large clinical databases by use of claims data is a potential strategy for improving efficiency while reducing study costs. We sought to compare the use of Medicare data with data from the Women's Health Initiative (WHI) to determine peripheral vascular events, as defined by the WHI study design.We studied participants from the WHI with both adjudicated outcomes and links to Medicare enrollment and utilization data through 2007. Outcomes of interest included hospitalizations for treatment of abdominal aortic aneurysm (AAA), lower extremity peripheral artery disease (LE PAD), and carotid artery stenosis (CAS). Events determined by WHI adjudication were compared with events defined by coding algorithms using diagnosis and procedure codes from Medicare data with a pilot data set and then validated with a test data set. We assessed agreement by a κ statistic and evaluated reasons for disagreement.In the pilot set, records from 50,511 participants were analyzed. Agreement between the Centers for Medicare and Medicaid Services and WHI for admissions with a diagnosis but no treatment procedures for vascular conditions was poor (κ, 0.02-0.18). On the basis of WHI outcome data collection, vascular treatment procedures occurred in 29 participants for AAA, 204 for LE PAD events, and 281 for CAS. Medicare hospital claims recorded 41 treatments for AAA, 255 for LE PAD, and 317 for CAS. For participants with a Centers for Medicare and Medicaid Services-captured vascular procedure and a record adjudicated by WHI, κ values for treatment procedures were 0.81 for AAA, 0.77 for PAD, and 0.93 for CAS. For vascular procedures identified by WHI but not by Medicare hospital data (n = 82), 55% were captured by Medicare physician claims. Conversely, for treatments identified by Medicare hospital data but not captured by WHI adjudication (n = 57), 74% had physician claims consistent with the procedure. Fifteen participants with AAA or LE PAD procedures in hospital claims had medical records available for review, and nine of these had definitive documentation of procedures that were not captured by the WHI adjudication process. Estimated positive predictive value of Medicare data was 91% to 94% for AAA, 92% to 95% for LE PAD, and 94% to 99% for CAS. Available test set data (n = 50,253) yielded generally similar results with κ of 0.77 for AAA, 0.79 for LE PAD, and 0.94 for CAS.Medicare data appear useful for identifying vascular treatment procedures for WHI participants. Medicare hospital claims identify more procedures than WHI does, with high positive predictive value, but also may not capture some procedures identified in WHI.

Abstract

Conclusive data about cardiovascular toxicity of nonsteroidal anti-inflammatory drugs (NSAIDs) are sparse. We hypothesized that regular NSAID use is associated with increased risk for cardiovascular events in postmenopausal women, and that this association is stronger with greater cyclooxygenase (cox)-2 when compared with cox-1 inhibition.Postmenopausal women enrolled in the Women's Health Initiative were classified as regular users or nonusers of nonaspirin NSAIDs. Cox regression examined NSAID use as a time-varying covariate and its association with the primary outcome of total cardiovascular disease defined as cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Secondary analyses considered the association of selective cox-2 inhibitors (eg, celecoxib), nonselective agents with cox-2>cox-1 inhibition (eg, naproxen), and nonselective agents with cox-1>cox-2 inhibition (eg, ibuprofen) with the primary outcome. Overall, 160 801 participants were available for analysis (mean follow-up, 11.2 years). Regular NSAID use at some point in time was reported by 53 142 participants. Regular NSAID use was associated with an increased hazard for cardiovascular events versus no NSAID use (hazard ratio [HR], 1.10; 95% confidence interval, 1.06-1.15; P<0.001). Selective cox-2 inhibitors were associated with a modest increased hazard for cardiovascular events (hazard ratio, 1.13; 1.04-1.23; P=0.004 and celecoxib only: HR, 1.13; 1.01-1.27; P=0.031). Among aspirin users, concomitant selective cox-2 inhibitor use was no longer associated with increased hazard for cardiovascular events. There was an increased risk for agents with cox-2>cox-1 inhibition (HR, 1.17; 1.10-1.24; P<0.001 and naproxen only: HR, 1.22; 1.12-1.34; P<0.001). This harmful association remained among concomitant aspirin users. We did not observe a risk elevation for agents with cox-1>cox-2 inhibition (HR, 1.01; 0.95-1.07; P=0.884 and ibuprofen only: HR, 1.00; 0.93-1.07; P=0.996).Regular use of selective cox-2 inhibitors and nonselective NSAIDs with cox-2>cox-1 inhibition showed a modestly increased hazard for cardiovascular events. Nonselective agents with cox-1>cox-2 inhibition were not associated with increased cardiovascular risk.www.clinicaltrials.gov. Unique identifier: NCT00000611.

Abstract

Recent studies that have assessed the comparative effectiveness between coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) in patients with end-stage renal disease (ESRD) that have included analyses of temporal trends in mortality have noted mixed results.We conducted an observational longitudinal cohort study of all adults with ESRD undergoing CABG or PCI within Kaiser Permanente Northern California. The primary predictor, index period of revascularization, was categorized into 3 periods: 1996-1999 (reference), 2000-2003, and 2004-2008, with the primary outcome being 3-year all-cause mortality. A multivariable Cox regression model with the assumption of independent censoring was used to determine the adjusted relative risk of the primary predictor.Among 1015 ESRD patients, 3-year mortality showed no significant change in the 2000-2003 period but was lower during the 2004-2008 period with an adjusted hazard ratio of 0.66 (95% confidence interval: 0.49-0.88; trend test p = 0.01). No change in 30-day mortality was noted. Further adjustment for receipt of medications at baseline and after revascularization did not materially affect risk estimates. No significant interactions were observed between the type of revascularization (CABG or PCI) and the period of the index revascularization.Among a high-risk cohort of patients with ESRD and coronary artery disease within Kaiser Permanente Northern California who were referred for coronary revascularization by either CABG or PCI, the relative risk of mortality in the 2004-2008 period decreased by 34% compared with the 1996-1999 period, with the benefit primarily in the decrease in late mortality.

Abstract

This study sought to examine the effectiveness of clopidogrel in real-world, medically managed patients with unstable angina (UA) or non-ST-segment elevation myocardial infarction (NSTEMI).Although clinical trials have demonstrated the efficacy of clopidogrel to reduce cardiovascular (CV) morbidity and mortality in medically managed patients with UA or NSTEMI, the effectiveness of clopidogrel in actual clinical practice is less certain.A retrospective cohort study was conducted of Kaiser Permanente Northern California members without known coronary artery disease or prior clopidogrel use who presented with UA or NSTEMI between 2003 and 2008 and were medically managed (i.e., no percutaneous coronary intervention or coronary artery bypass grafting during the index hospitalization or within 7 days post-discharge). Over 2 years of follow-up, we measured the association between clopidogrel use and all-cause mortality, hospital stay for MI, and a composite endpoint of death or MI using propensity-matched multivariable Cox analyses.We identified 16,365 patients with incident UA (35%) or NSTEMI (65%); 36% of these patients were prescribed clopidogrel within 7 days of discharge. In 8,562 propensity score-matched patients, clopidogrel users had lower rates of all-cause mortality (8.3% vs. 13.0%; p < 0.01; adjusted hazard ratio [HR]: 0.63; 95% confidence interval [CI]: 0.54 to 0.72) and the composite of death or MI (13.5% vs. 17.4%; p < 0.01; HR: 0.74, CI: 0.66 to 0.84), but not MI alone (6.7% vs. 7.2%; p = 0.30; HR: 0.93, CI: 0.78 to 1.11), compared with nonusers of clopidogrel. The association between clopidogrel use and the composite of death or MI was significant only among patients presenting with NSTEMI (HR: 0.67; CI: 0.59 to 0.76; pint < 0.01), not among those presenting with UA (HR: 1.25; CI: 0.94 to 1.67).In a large, community-based cohort of patients who were medically managed after UA/NSTEMI, clopidogrel use was associated with a lower risk of death and MI, particularly among patients with NSTEMI.

Abstract

The findings of the Women's Health Initiative (WHI) estrogen plus progestin (E+P) trial led to a substantial reduction in use of combined hormone therapy (cHT) among postmenopausal women in the United States. The economic effect of this shift has not been evaluated relative to the trial's $260 million cost (2012 U.S. dollars).To estimate the economic return from the WHI E+P trial.Decision model to simulate health outcomes for a "WHI scenario" with observed cHT use and a "no-WHI scenario" with cHT use extrapolated from the pretrial period.Primary analyses of WHI outcomes, peer-reviewed literature, and government sources.Postmenopausal women in the United States, aged 50 to 79 years, who did not have a hysterectomy.2003 to 2012.Payer.Combined hormone therapy.Disease incidence, expenditure, quality-adjusted life-years, and net economic return.The WHI scenario resulted in 4.3 million fewer cHT users, 126,000 fewer breast cancer cases, 76,000 fewer cardiovascular disease cases, 263,000 more fractures, 145,000 more quality-adjusted life-years, and expenditure savings of $35.2 billion. The corresponding net economic return of the trial was $37.1 billion ($140 per dollar invested in the trial) at a willingness-to-pay level of $100,000 per quality-adjusted life-year.The 95% CI for the net economic return of the trial was $23.1 to $51.2 billion.No evaluation of indirect costs or outcomes beyond 2012.The WHI E+P trial made high-value use of public funds with a substantial return on investment. These results can contribute to discussions about the role of public funding for large, prospective trials with high potential for public health effects.National Heart, Lung, and Blood Institute.

Abstract

The goal of this study was to compare the economic outcomes of patients undergoing different noninvasive tests to evaluate suspected coronary artery disease (CAD).Evaluation of noninvasive tests is shifting to an assessment of their effect on clinical outcomes rather than on their diagnostic accuracy. Economic outcomes of testing are particularly important in light of rising medical care costs.We used an observational registry of 1,703 patients who underwent coronary computed tomography angiography (CTA) (n = 590), positron emission tomography (PET) (n = 548), or single-photon emission computed tomography (SPECT) (n = 565) for diagnosis of suspected CAD at 1 of 41 centers. We followed patients for 2 years, and documented resource use, medical costs for CAD, and clinical outcomes. We used multivariable analysis and propensity score matching to control for differences in baseline characteristics.Two-year costs were highest after PET ($6,647, 95% confidence interval [CI]: $5,896 to $7,397), intermediate after CTA ($4,909, 95% CI: $4,378 to $5,440), and lowest after SPECT ($3,965, 95% CI: $3,520 to $4,411). After multivariable adjustment, CTA costs were 15% higher than SPECT (p < 0.01), and PET costs were 22% higher than SPECT (p < 0.0001). Two-year mortality was 0.7% after CTA, 1.6% after SPECT, and 5.5% after PET. The incremental cost-effectiveness ratio for CTA compared with SPECT was $11,700 per life-year added, but was uncertain, with higher costs and higher mortality in 13% of bootstrap replications. Patients undergoing PET had higher costs and higher mortality than patients undergoing SPECT in 98% of bootstrap replications.Costs were significantly lower after using SPECT rather than CTA or PET in the evaluation of suspected coronary disease. SPECT was economically attractive compared with PET, whereas CTA was associated with higher costs and no significant difference in mortality compared with SPECT.

Abstract

Screening and surveillance are recommended in the management of small abdominal aortic aneurysms (AAAs). Gaps in surveillance after early diagnosis may lead to unrecognized AAA growth, rupture, and death. This study investigates the frequency and predictors of rupture of previously diagnosed AAAs.Data were extracted from Medicare claims for patients who underwent AAA repair between 2006 and 2009. Relevant preoperative abdominal imaging exams were tabulated up to 5 years prior to AAA repair. Repair for ruptured AAAs was compared with repair for intact AAAs for those with an early diagnosis of an AAA, defined as having received imaging at least 6 months prior to surgery. Gaps in surveillance were defined as no image within 1 year of surgery or no imaging for more than a 2-year time span after the initial image. Logistic regression was used to examine independent predictors of rupture despite early diagnosis.A total of 9298 patients had repair after early diagnosis, with rupture occurring in 441 (4.7%). Those with ruptured AAAs were older (80.2 ± 6.9 vs 77.6 ± 6.2 years; P < .001), received fewer images prior to repair (5.7 ± 4.1 vs 6.5 ± 3.5; P = .001), were less likely to be treated in a high-volume hospital (45.4% vs 59.5%; P < .001), and were more likely to have had gaps in surveillance (47.4% vs 11.8%; P < .001) compared with those receiving repair for intact AAAs. After adjusting for medical comorbidities, gaps in surveillance remained the largest predictor of rupture in a multivariate analysis (odds ratio, 5.82; 95% confidence interval, 4.64-7.31; P < .001).Despite previous diagnosis of AAA, many patients experience rupture prior to repair. Improved mechanisms for surveillance are needed to prevent rupture and ensure timely repair for patients with AAAs.

Abstract

Clinical guidelines have been criticized for encouraging the use of β-blockers in noncardiac surgery despite weak evidence. Relevant clinical trials have been small and have not convincingly demonstrated an effect of β-blockers on hard end points (ie, perioperative myocardial infarction, ischemic stroke, cardiovascular death, and all-cause death).To assess the association of β-blocker treatment with major cardiovascular adverse events (MACE) and all-cause mortality in patients with ischemic heart disease undergoing noncardiac surgery. DESIGN, SETTING, PARTICIPANTS, AND EXPOSURE: Individuals with ischemic heart disease with or without heart failure (HF) and with and without a history of myocardial infarction undergoing noncardiac surgery between October 24, 2004, and December 31, 2009, were identified from nationwide Danish registries. Adjusted Cox regression models were used to calculate the 30-day risks of MACE (ischemic stroke, myocardial infarction, or cardiovascular death) and all-cause mortality associated with β-blocker therapy.Thirty-day risk of MACE and all-cause mortality.Of 28,263 patients with ischemic heart disease undergoing surgery, 7990 (28.3%) had HF and 20,273 (71.7%) did not. β-Blockers were used in 4262 (53.3%) with and 7419 (36.6%) without HF. Overall, use of β-blockers was associated with a hazard ratio (HR) of 0.90 (95% CI, 0.79-1.02) for MACE and 0.95 (0.85-1.06) for all-cause mortality. Among patients with HF, use of β-blockers was associated with a significantly lower risk of MACE (HR, 0.75; 95% CI, 0.70-0.87) and all-cause mortality (0.80; 0.70-0.92), whereas among patients without HF, there was no significant association of β-blocker use with MACE (1.11; 0.92-1.33) or mortality (1.15; 0.98-1.35) (P < .001 for interactions). Among patients without HF, β-blockers were also associated with a lowered risk among those with a recent myocardial infarction (<2 years), with HRs of 0.54 (95% CI, 0.37-0.78) for MACE and 0.80 (0.53-1.21) for all-cause mortality (P < .02 for interactions between β-blockers and time period after myocardial infarction), but with no significant association in the remaining patients. Results were similar in propensity score-matched analyses.Among patients with ischemic heart disease undergoing noncardiac surgery, use of β-blockers was associated with lower risk of 30-day MACE and mortality only among those with HF or recent myocardial infarction.

Abstract

Correctable weaknesses in the design, conduct, and analysis of biomedical and public health research studies can produce misleading results and waste valuable resources. Small effects can be difficult to distinguish from bias introduced by study design and analyses. An absence of detailed written protocols and poor documentation of research is common. Information obtained might not be useful or important, and statistical precision or power is often too low or used in a misleading way. Insufficient consideration might be given to both previous and continuing studies. Arbitrary choice of analyses and an overemphasis on random extremes might affect the reported findings. Several problems relate to the research workforce, including failure to involve experienced statisticians and methodologists, failure to train clinical researchers and laboratory scientists in research methods and design, and the involvement of stakeholders with conflicts of interest. Inadequate emphasis is placed on recording of research decisions and on reproducibility of research. Finally, reward systems incentivise quantity more than quality, and novelty more than reliability. We propose potential solutions for these problems, including improvements in protocols and documentation, consideration of evidence from studies in progress, standardisation of research efforts, optimisation and training of an experienced and non-conflicted scientific workforce, and reconsideration of scientific reward systems.

Abstract

The aim of this study was to assess the pattern of the adoption of internal mammary artery (IMA) grafting in the United States, test its association with clinical outcomes, and assess whether its effectiveness differs in key clinical subgroups.The effect of IMA grafting on major clinical outcomes has never been tested in a large randomized trial, yet it is now a quality standard for coronary artery bypass graft (CABG) surgery.We identified Medicare beneficiaries ≥66 years of age who underwent isolated multivessel CABG between 1988 and 2008, and we documented patterns of IMA use over time. We used a multivariable propensity score to match patients with and without an IMA and compared rates of death, myocardial infarction (MI), and repeat revascularization. We tested for variations in IMA effectiveness with treatment × covariate interaction tests.The IMA use in CABG rose slowly from 31% in 1988 to 91% in 2008, with persistent wide geographic variations. Among 60,896 propensity score-matched patients over a median 6.8-year follow-up, IMA use was associated with lower all-cause mortality (adjusted hazard ratio: 0.77, p < 0.001), lower death or MI (adjusted hazard ratio: 0.77, p < 0.001), and fewer repeat revascularizations over 5 years (8% vs. 9%, p < 0.001). The association between IMA use and lower mortality was significantly weaker (p ≤ 0.008) for older patients, women, and patients with diabetes or peripheral arterial disease.Internal mammary artery grafting was adopted slowly and still shows substantial geographic variation. IMA use is associated with lower rates of death, MI, and repeat coronary revascularization.

Abstract

Preoperative β-blockade has been posited to result in better outcomes for vascular surgery patients by attenuating acute hemodynamic changes associated with stress. However, the incremental effectiveness, if any, of β-blocker usage in blunting heart rate responsiveness for vascular surgery patients who avoid general anesthesia remains unknown.We reviewed an existing database and identified 213 consecutive vascular surgery cases from 2005-2011 conducted without general anesthesia (i.e., under monitored anesthesia care or regional anesthesia) at a tertiary care Veterans Administration medical center and categorized patients based on presence or absence of preoperative β-blocker prescription. For this series of patients, with the primary outcome of maximum heart rate during the interval between operating room entry to surgical incision, we examined the association of maximal heart rate and preoperative β-blocker usage by performing crude and multivariate linear regression, adjusting for relevant patient factors.Of 213 eligible cases, 137 were prescribed preoperative β-blockers, and 76 were not. The two groups were comparable across baseline patient factors and intraoperative medication doses. The β-blocker group experienced lower maximal heart rates during the period of evaluation compared to the non-β-blocker group (85 ± 22 bpm vs. 98 ± 36 bpm, respectively; p = 0.002). Adjusted linear regression confirmed a statistically-significant association between lower maximal heart rate and the use of β-blockers (Beta = -11.5; 95% CI [-3.7, -19.3] p = 0.004).The addition of preoperative β-blockers, even when general anesthesia is avoided, may be beneficial in further attenuating stress-induced hemodynamic changes for vascular surgery patients.

Abstract

Prognostic factors are usually evaluated by their statistical significance rather than by their clinical utility. Risk reclassification measures the extent to which a novel marker adds useful information to a prognostic model. The extent to which estimated glomerular filtration rate (eGFR) adds information about prognosis among patients with coronary heart disease is uncertain.We studied patients in an integrated health care delivery system with newly diagnosed coronary heart disease. We developed a model of the risk of death over 2 years of follow-up and then added eGFR to the model and measured changes in C-index, net reclassification improvement, and integrated discrimination improvement.Almost half of the 31,533 study patients had reduced eGFR (<60 mL/min per 1.73 m(2)). Mortality was significantly higher among patients who had lower levels of eGFR, even after adjustment for baseline characteristics (P < .0001). The addition of eGFR to the prognostic model increased the C-index from 0.837 to 0.843, the net reclassification improvement by 3.2% (P < .0001), and integrated discrimination improvement by 1.3% (P = .007).Estimated glomerular filtration rate is an informative prognostic factor among patients with incident coronary heart disease, independent of other clinical characteristics.

Abstract

Aldosterone receptor antagonists have been shown in randomized trials to reduce morbidity and mortality in adults with symptomatic systolic heart failure. We studied the effectiveness and safety of spironolactone in adults with newly diagnosed systolic heart failure in clinical practice. We identified all adults with newly diagnosed heart failure, left ventricular ejection fraction of <40%, and no previous spironolactone use from 2006 to 2008 in Kaiser Permanente Northern California. We excluded patients with baseline serum creatinine level of >2.5 mg/dl or a serum potassium level of >5.0 mEq/L. We used Cox regression with time-varying covariates to evaluate the independent association between spironolactone use and death, hospitalization, severe hyperkalemia, and acute kidney injury. Among 2,538 eligible patients with a median follow-up of 2.5 years, 521 patients (22%) initiated spironolactone, which was not associated with risk of hospitalization (adjusted hazard ratio 0.91, 95% confidence interval 0.77 to 1.08) or death (adjusted hazard ratio 0.93, confidence interval 0.60 to 1.44). Crude rates of severe hyperkalemia and acute kidney injury during spironolactone use were similar to that seen in clinical trials. Spironolactone was independently associated with a 3.5-fold increased risk of hyperkalemia but not with acute kidney injury. Within a diverse community-based cohort with incident systolic heart failure, use of spironolactone was not independently associated with risks of hospitalization or death. Our findings suggest that the benefits of spironolactone in clinical practice may be reduced compared with other guideline-recommended medications.

Abstract

Rheumatic disease and heart disease share common underpinnings involving inflammation. The high levels of inflammation that characterize rheumatic diseases provide a "natural experiment" to help elucidate the mechanisms by which inflammation accelerates heart disease. Rheumatoid arthritis (RA) is the most common of the rheumatic diseases and has the best studied relationships with heart disease.A review of current literature on heart disease and RA was conducted.Patients with RA have an increased risk of developing heart disease that is not fully explained by traditional cardiovascular risk factors. Therapies used to treat RA may also affect the development of heart disease; by suppressing inflammation, they may also reduce the risk of heart disease. However, their other effects, as in the case of steroids, may increase heart disease risk.Investigations of the innate and adaptive immune responses occurring in RA may delineate novel mechanisms in the pathogenesis of heart disease and help identify novel therapeutic targets for the prevention and treatment of heart disease.

Abstract

The Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (FAME) 2 trial demonstrated a significant reduction in subsequent coronary revascularization among patients with stable angina and at least 1 coronary lesion with a fractional flow reserve ≤0.80 who were randomized to percutaneous coronary intervention (PCI) compared with best medical therapy. The economic and quality-of-life implications of PCI in the setting of an abnormal fractional flow reserve are unknown.We calculated the cost of the index hospitalization based on initial resource use and follow-up costs based on Medicare reimbursements. We assessed patient utility using the EQ-5D health survey with US weights at baseline and 1 month and projected quality-adjusted life-years assuming a linear decline over 3 years in the 1-month utility improvements. We calculated the incremental cost-effectiveness ratio based on cumulative costs over 12 months. Initial costs were significantly higher for PCI in the setting of an abnormal fractional flow reserve than with medical therapy ($9927 versus $3900, P<0.001), but the $6027 difference narrowed over 1-year follow-up to $2883 (P<0.001), mostly because of the cost of subsequent revascularization procedures. Patient utility was improved more at 1 month with PCI than with medical therapy (0.054 versus 0.001 units, P<0.001). The incremental cost-effectiveness ratio of PCI was $36 000 per quality-adjusted life-year, which was robust in bootstrap replications and in sensitivity analyses.PCI of coronary lesions with reduced fractional flow reserve improves outcomes and appears economically attractive compared with best medical therapy among patients with stable angina.

Abstract

Clinical guidelines recommend digoxin for patients with symptomatic systolic heart failure (HF) receiving optimal medical therapy, but this recommendation is based on limited, older trial data. We evaluated the effectiveness and safety of digoxin in a contemporary cohort of patients with incident systolic HF.We identified adults with incident systolic HF between 2006 and 2008 within Kaiser Permanente Northern California who had no prior digoxin use. We used multivariable extended Cox regression to examine the association between new digoxin use and risks of death and HF hospitalization, controlling for medical history, laboratory results, medications, HF disease severity, and the propensity for digoxin use. We also conducted analyses stratified by sex and concurrent β-blocker use. Among 2891 newly diagnosed patients with systolic HF, 529 (18%) received digoxin. During a median 2.5 years of follow-up, incident digoxin use was associated with higher rates of death (14.2 versus 11.3 per 100 person-years) and HF hospitalization (28.2 versus 24.4 per 100 person-years). In multivariable analysis, incident digoxin use was associated with higher mortality (hazard ratio, 1.72; 95% confidence interval, 1.25-2.36) but no significant difference in the risk of HF hospitalization (hazard ratio, 1.05; 95% confidence interval, 0.82-1.34). Results were similar in analyses stratified by sex and β-blocker use.Digoxin use in patients with incident systolic HF was independently associated with a higher risk of death but no difference in HF hospitalization.

Abstract

Background- Transcatheter aortic valve replacement (TAVR) seems to improve the survival and quality of life of patients with aortic stenosis ineligible for surgical aortic valve replacement. Methods and Results- We used a decision analytic Markov model to estimate lifetime costs and benefits in a hypothetical cohort of patients with severe, symptomatic aortic stenosis who were ineligible for surgical aortic valve replacement. The model compared transfemoral TAVR with medical management and was calibrated to the Placement of Aortic Transcatheter Valves (PARTNER) trial. TAVR increased life expectancy from 2.08 to 2.93 years and quality-adjusted life expectancy from 1.19 to 1.93 years. TAVR also reduced subsequent hospitalizations by 1.40 but increased complications, particularly stroke (from 1% to 11% lifetime risk), and also increased lifetime costs from $83 600 to $1 69 100. The incremental cost-effectiveness of TAVR was $1 16 500 per quality-adjusted life-year gained ($99 900 per life-year gained). Results were robust to reasonable changes in individual variables but were sensitive to the level of annual healthcare costs caused by noncardiac diseases and to the projected life expectancy of medically treated patients. Conclusions- TAVR seems to be an effective but somewhat expensive alternative to medical management among patients with symptomatic aortic stenosis ineligible for surgery. TAVR is more cost-effective for patients with a lower burden of noncardiac disease.

Abstract

Abdominal aortic aneurysm (AAA) screening remains largely underutilized in the U.S., and it is likely that the proportion of patients with aneurysms requiring prompt treatment is much higher compared with well-screened populations. The goals of this study were to determine the proportion of AAAs that required prompt repair after diagnostic abdominal imaging for U.S. Medicare beneficiaries and to identify patient and hospital factors contributing to early vs late diagnosis of AAA.Data were extracted from Medicare claims records for patients at least 65 years old with complete coverage for 2 years who underwent intact AAA repair from 2006 to 2009. Preoperative ultrasound and computed tomography was tabulated from 2002 to repair. We defined early diagnosis of AAA as a patient with a time interval of greater than 6 months between the first imaging examination and the index procedure, and late diagnosis as patients who underwent the index procedure within 6 months of the first imaging examination.Of 17,626 patients who underwent AAA repair, 14,948 met inclusion criteria. Mean age was 77.5 ± 6.1 years. Early diagnosis was identified for 60.6% of patients receiving AAA repair, whereas 39.4% were repaired after a late diagnosis. Early diagnosis rates increased from 2006 to 2009 (59.8% to 63.4%; P < .0001) and were more common for intact repair compared with repair after rupture (62.9% vs 35.1%; P < .0001) and for women compared with men (66.3% vs 59.0%; P < .0001). On multivariate analysis, repair of intact vs ruptured AAAs (odds ratio, 3.1; 95% confidence interval, 2.7-3.6) and female sex (odds ratio, 1.4; 95% confidence interval, 1.3-1.5) remained the strongest predictors of surveillance. Although intact repairs were more likely to be diagnosed early, over one-third of patients undergoing repair for ruptured AAAs received diagnostic abdominal imaging greater than 6 months prior to surgery.Despite advances in screening practices, significant missed opportunities remain in the U.S. Medicare population for improving AAA care. It remains common for AAAs to be diagnosed when they are already at risk for rupture. In addition, a significant proportion of patients with early imaging rupture prior to repair. Our findings suggest that improved mechanisms for observational management are needed to ensure optimal preoperative care for patients with AAAs.

Abstract

Randomized clinical trials comparing coronary artery bypass grafting (CABG) with percutaneous coronary intervention (PCI) have largely excluded patients with chronic kidney disease (CKD), leading to uncertainty about the optimal coronary revascularization strategy. We sought to test the hypothesis that an initial strategy of CABG would be associated with lower risks of long-term mortality and cardiovascular morbidity compared with PCI for the treatment of multivessel coronary heart disease in the setting of CKD.We created a propensity score-matched cohort of patients aged ≥30 years with no prior dialysis or renal transplant who received multivessel coronary revascularization between 1996 and 2008 within a large integrated health care delivery system in northern California. We used extended Cox regression to examine death from any cause, acute coronary syndrome, and repeat revascularization.Coronary artery bypass grafting was associated with a significantly lower adjusted rate of death than PCI across all strata of estimated glomerular filtration rate (eGFR) (in mL/min per 1.73 m(2)): the adjusted hazard ratio (HR) was 0.81, 95% CI 0.68 to 1.00 for patients with eGFR ≥60; HR 0.73 (CI 0.56-0.95) for eGFR of 45 to 59; and HR 0.87 (CI 0.67-1.14) for eGFR <45. Coronary artery bypass grafting was also associated with significantly lower rates of acute coronary syndrome and repeat revascularization at all levels of eGFR compared with PCI.Among adults with and without CKD, multivessel CABG was associated with lower risks of death and coronary events compared with multivessel PCI.

Abstract

This study sought to ascertain the relationship of 9p21 locus with: 1) angiographic coronary artery disease (CAD) burden; and 2) myocardial infarction (MI) in individuals with underlying CAD.Chromosome 9p21 variants have been robustly associated with coronary heart disease, but questions remain on the mechanism of risk, specifically whether the locus contributes to coronary atheroma burden or plaque instability.We established a collaboration of 21 studies consisting of 33,673 subjects with information on both CAD (clinical or angiographic) and MI status along with 9p21 genotype. Tabular data are provided for each cohort on the presence and burden of angiographic CAD, MI cases with underlying CAD, and the diabetic status of all subjects.We first confirmed an association between 9p21 and CAD with angiographically defined cases and control subjects (pooled odds ratio [OR]: 1.31, 95% confidence interval [CI]: 1.20 to 1.43). Among subjects with angiographic CAD (n = 20,987), random-effects model identified an association with multivessel CAD, compared with those with single-vessel disease (OR: 1.10, 95% CI: 1.04 to 1.17)/copy of risk allele). Genotypic models showed an OR of 1.15, 95% CI: 1.04 to 1.26 for heterozygous carrier and OR: 1.23, 95% CI: 1.08 to 1.39 for homozygous carrier. Finally, there was no significant association between 9p21 and prevalent MI when both cases (n = 17,791) and control subjects (n = 15,882) had underlying CAD (OR: 0.99, 95% CI: 0.95 to 1.03)/risk allele.The 9p21 locus shows convincing association with greater burden of CAD but not with MI in the presence of underlying CAD. This adds further weight to the hypothesis that 9p21 locus primarily mediates an atherosclerotic phenotype.

Abstract

Establishing medication effectiveness outside of a randomized trial requires careful study design to mitigate selection bias. Previous observational studies of β-blockers in patients with chronic kidney disease and heart failure have had methodologic limitations that may have introduced bias. We examined whether initiation of β-blocker therapy was associated with better outcomes among patients with chronic kidney disease and newly diagnosed heart failure with left ventricular systolic dysfunction.We identified 668 adults in the Kaiser Permanente Northern California system from 2006 to 2008 with chronic kidney disease, incident heart failure, left ventricular systolic dysfunction, and no previous β-blocker use. We defined chronic kidney disease as estimated glomerular filtration rate <60 mL min(-1) 1.73 m(-2) or proteinuria, and we excluded patients receiving dialysis. We used extended Cox regression to assess the association of treatment with death and the combined end point of death or heart failure hospitalization. Initiation of β-blocker therapy was associated with a significantly lower crude risk of death (hazard ratio [HR] 0.47, 95% confidence interval [CI] 0.35-0.63), but this association was attenuated and no longer significant after multivariable adjustment (HR 0.75, CI 0.51-1.12). β-Blocker therapy was significantly associated with a lower risk of death or heart failure hospitalization even after adjustment for potential confounders (HR 0.67, CI 0.51-0.88).β-Blocker therapy is associated with lower risk of death or heart failure hospitalization among patients with chronic kidney disease, incident heart failure, and left ventricular systolic dysfunction.

Abstract

Procedure volume is potentially important for physicians learning a new procedure and for practicing physicians to maintain proficiency. Volume standards for training are largely based on opinion. In contrast, there are substantial data showing that the volume of procedures performed by a hospital or physician in practice has an inverse relationship with clinical outcomes: higher volumes are associated with better outcomes. Increased procedure volume for implantable defibrillators has been associated with lower short-term complication rates. The controversial policy implications of these observations are discussed.

Abstract

This study sought to compare use of evidence-based secondary preventive medications after coronary bypass surgery (CABG) and percutaneous coronary intervention (PCI).Use of cardioprotective medication after coronary revascularization has been inconsistent and relatively low in older studies.We studied patients in a large integrated healthcare delivery system who underwent CABG or PCI for new onset coronary disease. We used data from health plan databases about prescriptions dispensed during the first year after initial coronary revascularization to identify patients who never filled a prescription and to calculate the medication possession ratio among patients who filled at least 1 prescription. We focused on angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARBs), beta-blockers, and statins.Between 2000 and 2007, 8,837 patients with new onset coronary disease underwent initial CABG, and 14,516 underwent initial PCI. Patients receiving CABG were more likely than patients receiving PCI to not fill a prescription for a statin (7.1% vs. 4.8%, p < 0.0001) or for an ACEI/ARB (29.1% vs. 22.4%, p < 0.0001), but similar proportions never filled a prescription for a beta-blocker (6.4% vs. 6.1%). Among those who filled at least 1 prescription post-revascularization, patients receiving CABG had lower medication possession ratios than patients receiving PCI for ACEI/ARBs (69.4% vs. 77.8%, p < 0.0001), beta-blockers (76.1% vs. 80.6%, p < 0.0001), and statins (82.7% vs. 84.2%, p < 0.001).Patients who received CABG were generally less likely than patients who received PCI to fill prescriptions for secondary preventive medications and to use those medications consistently in the first year after the procedure.

Abstract

Observational methods are evolving in response to the widespread availability of data from clinical registries, electronic health records, and administrative databases. These approaches will never eliminate the need for randomized trials, but clearly have a role in evaluating the effect of therapies in unselected populations treated in routine practice.

Abstract

Thirty to sixty percent of patients with ESRD on dialysis have coronary heart disease, but the optimal strategy for coronary revascularization is unknown. We used data from the United States Renal Data System to define a cohort of 21,981 patients on maintenance dialysis who received initial coronary revascularization with either coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) between 1997 and 2009 and had at least 6 months of prior Medicare coverage as their primary payer. The primary outcome was death from any cause, and the secondary outcome was a composite of death or myocardial infarction. Overall survival rates were consistently poor during the study period, with unadjusted 5-year survival rates of 22%-25% irrespective of revascularization strategy. Using multivariable-adjusted proportional hazards regression, we found that CABG compared with PCI associated with significantly lower risks for both death (HR=0.87, 95% CI=0.84-0.90) and the composite of death or myocardial infarction (HR=0.88, 95% CI=0.86-0.91). Results were similar in analyses using a propensity score-matched cohort. In the absence of data from randomized trials, these results suggest that CABG may be preferred over PCI for multivessel coronary revascularization in appropriately selected patients on maintenance dialysis.

Abstract

This study sought to assess whether patient age modifies the comparative effectiveness of coronary artery bypass graft (CABG) surgery and percutaneous coronary intervention (PCI).Increasingly, CABG and PCI are performed in older patients to treat multivessel disease, but their comparative effectiveness is uncertain.Individual data from 7,812 patients randomized in 1 of 10 clinical trials of CABG or PCI were pooled. Age was analyzed as a continuous variable in the primary analysis and was divided into tertiles for descriptive purposes (≤56.2 years, 56.3 to 65.1 years, ≥65.2 years). The outcomes assessed were death, myocardial infarction and repeat revascularization over complete follow-up, and angina at 1 year.Older patients were more likely to have hypertension, diabetes, and 3-vessel disease compared with younger patients (p < 0.001 for trend). Over a median follow-up of 5.9 years, the effect of CABG versus PCI on mortality varied according to age (interaction p < 0.01), with adjusted CABG-to-PCI hazard ratios and 95% confidence intervals (CI) of 1.23 (95% CI: 0.95 to 1.59) in the youngest tertile; 0.89 (95% CI: 0.73 to 1.10) in the middle tertile; and 0.79 (95% CI: 0.67 to 0.94) in the oldest tertile. The CABG-to-PCI hazard ratio of less than 1 for patients 59 years of age and older. A similar interaction of age with treatment was present for the composite outcome of death or myocardial infarction. In contrast, patient age did not alter the comparative effectiveness of CABG and PCI on the outcomes of repeat revascularization or angina.Patient age modifies the comparative effectiveness of CABG and PCI on hard cardiac events, with CABG favored at older ages and PCI favored at younger ages.

Abstract

One sixth of US dialysis patients 65 years of age have been diagnosed with atrial fibrillation/flutter (AF). Little is known, however, about the incidence of AF in this population.We identified 258 605 older patients (≥67 years of age) with fee-for-service Medicare initiating dialysis in 1995 to 2007, who had not been diagnosed with AF within the previous 2 years. Patients were followed for newly diagnosed AF. Multivariable proportional hazard regression was used to examine temporal trends and associations of race and ethnicity with incident AF. We also studied temporal trends in the mortality and risk of ischemic stroke after new AF. Over 514 395 person-years of follow-up, 76 252 patients experienced incident AF for a crude AF incidence rate of 148/1000 person-years. Incidence of AF increased by 11% (95% confidence interval, 5-16) from 1995 to 2007. Compared with non-Hispanic whites, blacks (-30%), Asians (-19%), Native Americans (-42%), and Hispanics (-29%) all had lower rates of incident AF. Mortality after incident AF decreased by 22% from 1995 to 2008. Even more pronounced reductions were seen for incident ischemic stroke during these years.The incidence of AF is high in older patients initiating dialysis in the United States and has been increasing over the 13 years of study. Mortality declined during that time but remained >50% during the first year after newly diagnosed AF. Because data on warfarin use were not available, we were unable to study whether trends toward better outcomes could be explained by higher rates of oral anticoagulation.

Abstract

Since January 1, 2007, Medicare has covered abdominal aortic aneurysm (AAA) screening for new male enrollees with a history of smoking under the Screening Abdominal Aortic Aneurysms Very Efficiently (SAAAVE) Act. We examined the association between this program and abdominal ultrasonography for AAA screening, elective AAA repair, hospitalization for AAA rupture, and all-cause mortality.We used a 20% sample of traditional Medicare enrollees from 2004 to 2008 to identify 65-year-old men eligible for screening and 3 control groups not eligible for screening (70-year-old men, 76-year-old men, and 65-year-old women). We used logistic regression to examine the change in outcomes at 365 days for eligible vs ineligible beneficiaries before and after SAAAVE Act implementation, adjusting for comorbidities, state-level smoking prevalence, geographic variation, and time trends.Fewer than 3% of abdominal ultrasonography claims after 2007 were for SAAAVE-specific AAA screening. There was a significantly greater increase in abdominal ultrasonography use among SAAAVE-eligible beneficiaries (2.0 percentage points among 65-year-old men, from 7.6% in 2004 to 9.6% in 2008; 0.7 points [8.9% to 9.6%] among 70-year-old men; 0.7 points [10.8% to 11.5%] among 76-year-old men; and 0.9 points [7.5% to 8.4%] among 65-year-old women) (P < .001 for all comparisons with 65-year-old men). The SAAAVE Act was associated with increased use of abdominal ultrasonography in 65-year-old men compared with 70-year-old men (adjusted odds ratio [AOR], 1.15; 95% CI, 1.11-1.19) (P < .001), and this increased use remained even when SAAAVE-specific AAA screening was excluded (AOR, 1.12; 95% CI, 1.08-1.16) (P < .001). Implementation of the SAAAVE Act was not associated with changes in rates of AAA repair, AAA rupture, or all-cause mortality.The impact of the SAAAVE Act on AAA screening was modest and was based on abdominal ultrasonography use that it did not directly reimburse. The SAAAVE Act had no discernable effect on AAA rupture or all-cause morality.

Abstract

The Second Medicine, Angioplasty, or Surgery Study (MASS II) included patients with multivessel coronary artery disease and normal systolic ventricular function. Patients underwent coronary artery bypass graft surgery (CABG, n=203), percutaneous coronary intervention (PCI, n=205), or medical treatment alone (MT, n=203). This investigation compares the economic outcome at 5-year follow-up of the 3 therapeutic strategies.We analyzed cumulative costs during a 5-year follow-up period. To analyze the cost-effectiveness, adjustment was made on the cumulative costs for average event-free time and angina-free proportion. Respectively, for event-free survival and event plus angina-free survival, MT presented 3.79 quality-adjusted life-years and 2.07 quality-adjusted life-years; PCI presented 3.59 and 2.77 quality-adjusted life-years; and CABG demonstrated 4.4 and 2.81 quality-adjusted life-years. The event-free costs were $9071.00 for MT; $19,967.00 for PCI; and $18,263.00 for CABG. The paired comparison of the event-free costs showed that there was a significant difference favoring MT versus PCI (P<0.01) and versus CABG (P<0.01) and CABG versus PCI (P=0.01). The event-free plus angina-free costs were $16,553.00, $25,831.00, and $24,614.00, respectively. The paired comparison of the event-free plus angina-free costs showed that there was a significant difference favoring MT versus PCI (P=0.04), and versus CABG (P<0.001); there was no difference between CABG and PCI (P>0.05).In the long-term economic analysis, for the prevention of a composite primary end point, MT was more cost effective than CABG, and CABG was more cost-effective than PCI.www.controlled-trials.com.ISRCTN66068876.

Abstract

Comparative effectiveness research (CER) aims to provide decision makers with the evidence needed to evaluate the benefits and harms of alternative clinical management strategies. CER has become a national priority, with considerable new research funding allocated. Cardiovascular disease is a priority area for CER. This workshop report provides an overview of CER methods, with an emphasis on practical clinical trials and observational treatment comparisons. The report also details recommendations to the National Heart, Lung, and Blood Institute for a new framework for evidence development to foster cardiovascular CER, and specific studies to address 8 clinical issues identified by the Institute of Medicine as high priorities for cardiovascular CER.

Abstract

To investigate the association of preoperative β-blocker usage and maximal heart rates observed during the induction of general anesthesia.Retrospective descriptive, univariate, and multivariate analyses of electronic hospital and anesthesia medical records.A tertiary-care medical center within the Veterans Health Administration.Consecutive adult elective and emergent patients presenting for vascular surgery during calendar years 2005 to 2011.None.Of the 430 eligible cases, 218 were prescribed β-blockers, and 212 were not taking β-blockers. The two groups were comparable across baseline patient factors (ie, demographic, morphometric, surgical duration, and surgical procedures) and induction medication doses. The β-blocker group experienced a lower maximal heart rate during the induction of general anesthesia compared with the non-β-blocker group (105 ± 41 beats/min v 115 ± 45 beats/min, respectively; p < 0.01). Adjusted linear regression found a statistically significant association between lower maximal heart rate and the use of β-blockers (β = -11.1 beats/min, p < 0.01). There was no difference between groups in total intraoperative β-blocker administration.Preoperative β-blockade of vascular surgery patients undergoing general anesthesia is associated with a lower maximal heart rate during anesthetic induction. There may be potential benefits in administering β-blockers to reduce physiologic stress in this surgical population at risk for perioperative cardiac morbidity. Future research should further explore intraoperative hemodynamic effects in light of existing practice guidelines for optimal medication selection, dosage, and heart rate control.

Abstract

This study examined short-term cardiac catheterization rates and medication changes after cardiac imaging.Noninvasive cardiac imaging is widely used in coronary artery disease, but its effects on subsequent patient management are unclear.We assessed the 90-day post-test rates of catheterization and medication changes in a prospective registry of 1,703 patients without a documented history of coronary artery disease and an intermediate to high likelihood of coronary artery disease undergoing cardiac single-photon emission computed tomography, positron emission tomography, or 64-slice coronary computed tomography angiography.Baseline medication use was relatively infrequent. At 90 days, 9.6% of patients underwent catheterization. The rates of catheterization and medication changes increased in proportion to test abnormality findings. Among patients with the most severe test result findings, 38% to 61% were not referred to catheterization, 20% to 30% were not receiving aspirin, 35% to 44% were not receiving a beta-blocker, and 20% to 25% were not receiving a lipid-lowering agent at 90 days after the index test. Risk-adjusted analyses revealed that compared with stress single-photon emission computed tomography or positron emission tomography, changes in aspirin and lipid-lowering agent use was greater after computed tomography angiography, as was the 90-day catheterization referral rate in the setting of normal/nonobstructive and mildly abnormal test results.Overall, noninvasive testing had only a modest impact on clinical management of patients referred for clinical testing. Although post-imaging use of cardiac catheterization and medical therapy increased in proportion to the degree of abnormality findings, the frequency of catheterization and medication change suggests possible undertreatment of higher risk patients. Patients were more likely to undergo cardiac catheterization after computed tomography angiography than after single-photon emission computed tomography or positron emission tomography after normal/nonobstructive and mildly abnormal study findings. (Study of Perfusion and Anatomy's Role in Coronary Artery [CAD] [SPARC]; NCT00321399).

Abstract

The purpose of this study was to estimate rates and identify predictors of inpatient complications and 30-day readmissions, as well as repeat hospitalization rates for arrhythmia recurrence following atrial fibrillation (AF) ablation.AF is the most common clinically significant arrhythmia and is associated with increased morbidity and mortality. Radiofrequency or cryotherapy ablation of AF is a relatively new treatment option, and data on post-procedural outcomes in large general populations are limited.Using data from the California State Inpatient Database, we identified all adult patients who underwent their first AF ablation from 2005 to 2008. We used multivariable logistic regression to identify predictors of complications and/or 30-day readmissions and Kaplan-Meier analyses to estimate rates of all-cause and arrhythmia readmissions.Among 4,156 patients who underwent an initial AF ablation, 5% had periprocedural complications, most commonly vascular, and 9% were readmitted within 30 days. Older age, female, prior AF hospitalizations, and less hospital experience with AF ablation were associated with higher adjusted risk of complications and/or 30-day readmissions. The rate of all-cause hospitalization was 38.5% by 1 year. The rate of readmission for recurrent AF, atrial flutter, and/or repeat ablation was 21.7% by 1 year and 29.6% by 2 years.Periprocedural complications occurred in 1 of 20 patients undergoing AF ablation, and all-cause and arrhythmia-related rehospitalizations were common. Older age, female sex, prior AF hospitalizations, and recent hospital procedure experience were associated with a higher risk of complications and/or 30-day readmission after AF ablation.

Abstract

The outcomes of procedures are often better when they are performed by more experienced physicians. We assessed whether the rate of complications after implantable cardioverter-defibrillator (ICD) placement varied with the volume of procedures a physician performed.We studied 356 515 initial ICD implantations in the National Cardiovascular Data Registry-ICD Registry, performed by 4011 physicians in 1463 hospitals. We examined the relationship between physician annual ICD implantation volume and in-hospital complications, using hierarchical logistic regression to adjust for patient characteristics, implanting physician certification, hospital characteristics, hospital annual procedure volume, and the clustering of patients within hospitals and by physician. We repeated this analysis for ICD subtypes: single chamber, dual chamber, and biventricular. There were 10 994 patients (3.1%) with a complication after ICD implantation, and 1375 died (0.39%). The complication rate decreased with increasing physician procedure volume from 4.6% in the lowest quartile to 2.9% in the highest quartile (P<0.0001), and the mortality rate decreased from 0.72% to 0.36% (P<0.0001). The inverse relationship between physician procedure volume and complications remained significant after adjusting for patient, physician, and hospital characteristics (OR 1.55 for complications in lowest-volume quartile compared with highest; 95% confidence interval, 1.34-1.79; P<0.0001). This inverse relationship was independent of physician specialty and of hospital volume, was consistent across ICD subtypes, and was also evident for in-hospital mortality.Physicians who implant more ICDs have lower rates of procedural complications and in-hospital mortality, independent of hospital procedure volume, physician specialty, and ICD type.

Abstract

The aim of this study was to examine whether kidney dysfunction is associated with the type of clinical presentation of coronary heart disease (CHD).Reduced kidney function increases the risk for developing CHD, but it is not known whether it also influences the acuity of clinical presentation, which has important prognostic implications.A case-control study was conducted of subjects whose first clinical presentation of CHD was either acute myocardial infarction or stable exertional angina between October 2001 and December 2003. Estimated glomerular filtration rate (eGFR) before the incident event was calculated using calibrated serum creatinine and the abbreviated MDRD (Modification of Diet in Renal Disease) equation. Patient characteristics and use of medications were ascertained from self-report and health plan databases. Multivariable logistic regression was used to examine the association of reduced eGFR and CHD presentation.A total of 803 adults with incident acute myocardial infarctions and 419 adults with incident stable exertional angina who had baseline eGFRs ≤130 ml/min/1.73 m(2) were studied. Mean eGFR was lower in subjects with acute myocardial infarctions compared with those with stable angina. Compared with eGFR of 90 to 130 ml/min/1.73 m(2), a strong, graded, independent association was found between reduced eGFR and presenting with acute myocardial infarction, with adjusted odds ratios of 1.36 (95% confidence interval: 0.99 to 1.86) for eGFR 60 to 89 ml/min/1.73 m(2), 1.55 (95% confidence interval: 0.92 to 2.62) for eGFR 45 to 59 ml/min/1.73 m(2), and 3.82 (95% confidence interval: 1.55 to 9.46) for eGFR <45 ml/min/1.73 m(2) (p < 0.001 for trend).An eGFR <45 ml/min/1.73 m(2) is a strong, independent predictor of presenting with acute myocardial infarction versus stable angina as the initial manifestation of CHD.

Abstract

We sought to compare long-term outcomes after coronary bypass surgery with and without an internal thoracic artery graft.We analyzed clinical outcomes over a median follow-up of 6.7 years among 3,087 patients who received coronary bypass surgery as participants in one of 8 clinical trials comparing surgical intervention with angioplasty. We used 2 statistical methods (covariate adjustment and propensity score matching) to adjust for the nonrandomized selection of internal thoracic artery grafts.Internal thoracic artery grafting was associated with lower mortality, with hazard ratios of 0.77 (confidence interval, 0.62-0.97; P = .02) for covariate adjustment and 0.77 (confidence interval, 0.57-1.05; P = .10) for propensity score matching. The composite end point of death or myocardial infarction was reduced to a similar extent, with hazard ratios of 0.83 (confidence interval, 0.69-1.00; P = .05) for covariate adjustment to 0.78 (confidence interval, 0.61-1.00; P = .05) for propensity score matching. There was a trend toward less angina at 1 year, with odds ratios of 0.81 (confidence interval, 0.61-1.09; P = .16) in the covariate-adjusted model and 0.81 (confidence interval, 0.55-1.19; P = .28) in the propensity score-adjusted model.Use of an internal thoracic artery graft during coronary bypass surgery seems to improve long-term clinical outcomes.

Abstract

Bivalirudin is commonly used during percutaneous coronary intervention (PCI) rather than unfractionated heparin. The higher cost of bivalirudin may be offset if it reduces costly bleeding complications and/or length of stay. We sought to assess the effect of using bivalirudin on the costs of care among patients with ST-segment elevation myocardial infarction (STEMI) undergoing PCI.We analyzed data from 64,872 patients treated in 1 of 278 hospitals. The effect of overall hospital use of bivalirudin on clinical and economic outcomes was assessed using multivariable regression, based on average hospital use of treatments.The use of bivalirudin among patients with STEMI treated with PCI varied widely across hospitals, with a median of 6.9% (interquartile range 2.3%-18.6%). After controlling for patient and hospital characteristics, use of bivalirudin rather than heparin and a glycoprotein IIb/IIIa inhibitor reduced bleeding (odds ratio 0.47, P < .001), length of stay (-0.47 days, P < .03), and hospital costs (-14%, P < .04).Use of bivalirudin among patients with STEMI treated with PCI appears to reduce bleeding and overall costs.

Abstract

• The rapid and continuing progress in gene discovery for complex diseases is fuelling interest in the potential application of genetic risk models for clinical and public health practice. • The number of studies assessing the predictive ability is steadily increasing, but they vary widely in completeness of reporting and apparent quality. • Transparent reporting of the strengths and weaknesses of these studies is important to facilitate the accumulation of evidence on genetic risk prediction. • A multidisciplinary workshop sponsored by the Human Genome Epidemiology Network developed a checklist of 25 items recommended for strengthening the reporting of Genetic RIsk Prediction Studies (GRIPS), building on the principles established by prior reporting guidelines. • These recommendations aim to enhance the transparency, quality and completeness of study reporting and thereby to improve the synthesis and application of information from multiple studies that might differ in design, conduct or analysis.

Abstract

The purpose of this study was to determine the extent to which effectiveness of cardiac and diabetes treatment strategies varies by patient age.The impact of age on the effectiveness of revascularization and hyperglycemia treatments has not been thoroughly investigated.In the BARI 2D (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes) trial, 2,368 patients with documented stable heart disease and type 2 diabetes were randomized to receive prompt revascularization versus initial medical therapy with deferred revascularization and insulin sensitization versus insulin provision for hyperglycemia treatment. Patients were followed for an average of 5.3 years. Cox regression and mixed models were used to investigate the effect of age and randomized treatment assignment on clinical and health status outcomes.The effect of prompt revascularization versus medical therapy did not differ by age for death (interaction p = 0.99), major cardiovascular events (interaction p = 0.081), angina (interaction p = 0.98), or health status outcomes. After intervention, participants of all ages had significant angina and health status improvement. Younger participants experienced a smaller decline in health status during follow-up than older participants (age by time interaction p < 0.01). The effect of the randomized glycemia treatment on clinical and health status outcomes was similar for patients of different ages.Among patients with stable heart disease and type 2 diabetes, the relative beneficial effects of a strategy of prompt revascularization versus initial medical therapy and insulin-sensitizing versus insulin-providing therapy on clinical endpoints, symptom relief, and perceived health status outcomes do not vary by age. Health status improved significantly after treatment for all ages, and this improvement was sustained longer among younger patients. (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes [BARI 2D]; NCT00006305).

Abstract

The rapid and continuing progress in gene discovery for complex diseases is fuelling interest in the potential application of genetic risk models for clinical and public health practice. The number of studies assessing the predictive ability is steadily increasing, but they vary widely in completeness of reporting and apparent quality. Transparent reporting of the strengths and weaknesses of these studies is important to facilitate the accumulation of evidence on genetic risk prediction. A multidisciplinary workshop sponsored by the Human Genome Epidemiology Network developed a checklist of 25 items recommended for strengthening the reporting of Genetic RIsk Prediction Studies (GRIPS), building on the principles established by prior reporting guidelines. These recommendations aim to enhance the transparency, quality and completeness of study reporting, and thereby to improve the synthesis and application of information from multiple studies that might differ in design, conduct or analysis.

Abstract

The longitudinal association between obesity, weight variability, and health status outcomes is important for patients with coronary disease and diabetes.The BARI 2D was a multicenter randomized clinical trial designed to evaluate treatment strategies for patients with both documented stable ischemic heart disease and type 2 diabetes. We examined BARI 2D participants for 4 years to study how body mass index (BMI) was associated with health status outcomes. Health status was evaluated by the Duke Activity Status Index (DASI), RAND Energy/fatigue, Health Distress, and Self-rated Health. Body mass index was measured quarterly throughout follow-up years, and health status was assessed at each annual follow-up visit. Variation in BMI measures was separated into between-person and within-person change in longitudinal analysis.Higher mean BMI during follow-up years (the between-person BMI) was associated with poorer health status outcomes. Decreasing BMI (the within-person BMI change) was associated with better Self-rated health. The relationships between BMI variability and DASI or Energy appeared to be curvilinear and differed by baseline obesity status. Decreasing BMI was associated with better outcomes if patients were obese at baseline but was associated with poorer DASI and Energy outcomes if patients were nonobese at baseline.For patients with stable ischemic heart disease and diabetes, weight gain was associated with poorer health status outcomes, independent of obesity-related comorbidities. Weight reduction is associated with better functional capacity and perceived energy for obese patients but not for nonobese patients at baseline.

Abstract

Lipoprotein-associated phospholipase A₂ (Lp-PLA₂) is a predictor of cardiovascular events that has been shown to vary with race. The objective of this study was to examine factors associated with this racial variation.We measured Lp-PLA₂ mass and activity in 714 healthy older adults with no clinical coronary heart disease and not taking dyslipidemia medication. We evaluated the association between race and Lp-PLA₂ mass and activity levels after adjustment for various covariates using multivariable linear regression. These covariates included age, sex, diabetes, hypertension, body mass index, lipid measurements, C-reactive protein, smoking status, physical activity, diet, income, and education level. We further examined genetic covariates that included three single nucleotide polymorphisms shown to be associated with Lp-PLA₂ activity levels.The mean age was 66 years. Whites had the highest Lp-PLA₂ mass and activity levels, followed by Hispanics and Asians, and then African-Americans; in age and sex adjusted analyses, these differences were significant for each non-White race as compared to Whites (p < 0.0001). For example, African-Americans were predicted to have a 55.0 ng/ml lower Lp-PLA₂ mass and 24.7 nmol/ml-min lower activity, compared with Whites, independent of age and sex (p < 0.0001). After adjustment for all covariates, race remained significantly correlated with Lp-PLA₂ mass and activity levels (p < 0.001) with African-Americans having 44.8 ng/ml lower Lp-PLA₂ mass and 17.3 nmol/ml-min lower activity compared with Whites (p < 0.0001).Biological, lifestyle, demographic, and select genetic factors do not appear to explain variations in Lp-PLA₂ mass and activity levels between Whites and non-Whites, suggesting that Lp-PLA₂ mass and activity levels may need to be interpreted differently for various races.

Abstract

We investigated the association between physical activity and coronary vasodilation to nitroglycerin (NTG) in the ADVANCE (Atherosclerotic Disease, Vascular Function, and Genetic Epidemiology) cohort of older healthy subjects.Physical activity may exert its beneficial effects by augmenting coronary responsiveness to nitric oxide. The relationship between physical activity and coronary vasodilatory response to NTG, an exogenous nitric oxide donor, has not been studied in a community-based population with typical activity levels.In 212 older adults (ages 60 to 72 years) without cardiovascular disease, we measured the coronary vasodilatory response to NTG using magnetic resonance angiography and physical activity using the Stanford Seven-Day Physical Activity Recall Questionnaire. The primary predictor measure was total physical activity (kcal/kg/day). The primary outcome measure was coronary vasodilatory response (percent increase of cross-sectional area post-NTG).Coronary vasodilation was 27.6% in more active subjects (>35 kcal/kg/day, e.g., 1 h of walking per day) compared to 18.9% in less active subjects (p=0.03). Regression analysis showed a significant positive correlation between coronary vasodilation and physical activity (p=0.003), with a slope (beta) of 1.2% per kcal/kg/day. This finding remained significant after adjustment for cardiac risk factors, coronary calcium, the use of vasoactive or statin medications, and analysis of physical activity by quintiles (p < 0.05). Coronary vasodilation was also associated with physical activity intensity (p = 0.03).In an asymptomatic, community-based cohort of older adults, increased coronary vasodilatory response was independently associated with greater physical activity, supporting the benefits of exercise on the order of 1 h of walking per day.

Abstract

Screening for peripheral arterial disease (PAD) by measuring ankle brachial index (ABI) in asymptomatic older adults is currently recommended to improve cardiovascular disease risk assessment and establish early treatment, but it is not clear if the strategy is useful in all populations. We examined the prevalence and independent predictors of an abnormal ABI (<0.90), in an asymptomatic sample of 1,017 adults, 60 to 69 years old, enrolled in the ADVANCE study.Baseline data collected between December 2001 and January 2004 among the healthy older controls enrolled in ADVANCE was examined. Frequency distributions and prevalence estimates of an abnormal ABI were calculated, using both standard and modified definitions of ABI. Stepwise logistic regression was used to examine independent predictors of ABI <0.90. Signal detection analysis using recursive partitioning was employed to explore potential demographic and clinical variables related to ABI <0.90.The prevalence of ABI <0.90 was 2% when using the standard definition and 5% when using a modified definition. ABI prevalence did not differ by gender (P > .05). Compared with subjects who had a normal ABI (0.90-1.39), subjects with an ABI <0.90 were more likely to currently smoke, be physically inactive, have a coronary artery calcium score >10, and an FRS >20% (P ≤ .02). Independent predictors of ABI <0.90 when using the standard definition included currently smoking, physical inactivity, and body mass index >30 (all P values ≤.03), and when using the modified definition included currently smoking, physical inactivity, and hypertension (all P values ≤.04). Currently, smoking was the only significant variable for ABI <0.90 derived through recursive partitioning (P = .02), and indicated that prevalence of ABI <0.90 was 1.5% for nonsmokers, while it was 6.6% for current smokers.ABI screening in generally healthy individuals 60 to 69 years old may result in lower prevalence rates of a positive result than estimates based on studies in clinical populations. The modified definition for calculating ABI captured more asymptomatic adults with suspected peripheral arterial disease. More evaluation of the appropriate role of ABI screening in unselected populations is needed before routine screening is implemented.

Abstract

Racial and ethnic disparities are well documented in many areas of health care, but have not been comprehensively evaluated among recipients of heart transplants.We performed a retrospective cohort study of 39075 adult primary heart transplant recipients from 1987 to 2009 using national data from the United Network of Organ Sharing and compared mortality for nonwhite and white patients using the Cox proportional hazards model. During the study period, 8082 nonwhite and 30 993 white patients underwent heart transplantation. Nonwhite heart transplant recipients increased over time, comprising nearly 30% of transplantations since 2005. Nonwhite recipients had a higher clinical risk profile than white recipients at the time of transplantation, but had significantly higher posttransplantation mortality even after adjustment for baseline risk. Among the nonwhite group, only black recipients had an increased risk of death compared with white recipients after multivariable adjustment for recipient, transplant, and socioeconomic factors (hazard ratio, 1.34; 95% confidence interval, 1.21 to 1.47; P<0.001). Five-year mortality was 35.7% (95% confidence interval, 35.2 to 38.3) among black and 26.5% (95% confidence interval, 26.0 to 27.0) among white recipients. Black patients were more likely to die of graft failure or a cardiovascular cause than white patients, but less likely to die of infection or malignancy. Although mortality decreased over time for all transplant recipients, the disparity in mortality between blacks and whites remained essentially unchanged.Black heart transplant recipients have had persistently higher mortality than whites recipients over the past 2 decades, perhaps because of a higher rate of graft failure.

The Cost-Effectiveness of Rosuvastatin Therapy JUPITER (Justification for the Use of statins in Prevention: An Intervention Trial Evaluating Rosuvastatin)JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGYHlatky, M.2011; 57 (7): 792-793

Abstract

Family members of patients with established long-QT syndrome (LQTS) often lack definitive clinical findings, yet may have inherited an LQTS mutation and be at risk of sudden death. Genetic testing can identify mutations in 75% of patients with LQTS, but genetic testing of family members remains controversial.We used a Markov model to assess the cost-effectiveness of 3 strategies for treating an asymptomatic 10-year-old, first-degree relative of a patient with clinically evident LQTS. In the genetic testing strategy, relatives undergo genetic testing only for the mutation identified in the index patient, and relatives who test positive for the mutation are treated with β-blockers. This strategy was compared with (1) empirical treatment of relatives with β-blockers and (2) watchful waiting, with treatment only after development of symptoms. The genetic testing strategy resulted in better survival and quality-adjusted life years at higher cost, with a cost-effectiveness ratio of $67 400 per quality-adjusted life year gained compared with watchful waiting. The cost-effectiveness of the genetic testing strategy improved to less than $50 000 per quality-adjusted life year gained when applied selectively either to (1) relatives with higher clinical suspicion of LQTS (pretest probability 65% to 81%), or to (2) families with a higher than average risk of sudden death, or to (3) larger families (2 or more first-degree relatives tested).Genetic testing of young first-degree relatives of patients with definite LQTS is moderately expensive, but can reach acceptable thresholds of cost-effectiveness when applied to selected patients.

Abstract

We sought to replicate the association between the kinesin-like protein 6 (KIF6) Trp719Arg polymorphism (rs20455), and clinical coronary artery disease (CAD).Recent prospective studies suggest that carriers of the 719Arg allele in KIF6 are at increased risk of clinical CAD compared with noncarriers.The KIF6 Trp719Arg polymorphism (rs20455) was genotyped in 19 case-control studies of nonfatal CAD either as part of a genome-wide association study or in a formal attempt to replicate the initial positive reports.A total of 17,000 cases and 39,369 controls of European descent as well as a modest number of South Asians, African Americans, Hispanics, East Asians, and admixed cases and controls were successfully genotyped. None of the 19 studies demonstrated an increased risk of CAD in carriers of the 719Arg allele compared with noncarriers. Regression analyses and fixed-effects meta-analyses ruled out with high degree of confidence an increase of ≥2% in the risk of CAD among European 719Arg carriers. We also observed no increase in the risk of CAD among 719Arg carriers in the subset of Europeans with early-onset disease (younger than 50 years of age for men and younger than 60 years of age for women) compared with similarly aged controls as well as all non-European subgroups.The KIF6 Trp719Arg polymorphism was not associated with the risk of clinical CAD in this large replication study.

Abstract

We sought to examine the relationship between hospital implantable cardioverter-defibrillator (ICD) implantation volume and procedural complications in a contemporary, representative population.Hospitals that perform higher volumes of procedures generally have better clinical outcomes.We examined initial ICD implantations between January 2006 and December 2008 at hospitals participating in the NCDR (National Cardiovascular Data Registry) ICD Registry and evaluated the relationship between hospital annual implant volume and in-hospital adverse outcomes.The rate of adverse events declined progressively with increasing procedure volume (p trend < 0.0001). This relationship remained significant (p trend < 0.0001) after adjustment for patient clinical characteristics, operator characteristics, and hospital characteristics. The volume-outcome relationship was evident for all ICD subtypes, including single-chamber (p trend = 0.004), dual-chamber (p trend < 0.0001), and biventricular ICDs (p trend = 0.02).Patients who have an ICD implanted at a high-volume hospital are less likely to have an adverse event associated with the procedure than patients who have an ICD implanted at a low-volume hospital.

Abstract

Inclusion of 12-lead electrocardiography (ECG) in preparticipation screening of young athletes is controversial because of concerns about cost-effectiveness.To evaluate the cost-effectiveness of ECG plus cardiovascular-focused history and physical examination compared with cardiovascular-focused history and physical examination alone for preparticipation screening.Decision-analysis, cost-effectiveness model.Published epidemiologic and preparticipation screening data, vital statistics, and other publicly available data.Competitive athletes in high school and college aged 14 to 22 years.Lifetime.Societal.Nonparticipation in competitive athletic activity and disease-specific treatment for identified athletes with heart disease.Incremental health care cost per life-year gained.Addition of ECG to preparticipation screening saves 2.06 life-years per 1000 athletes at an incremental total cost of $89 per athlete and yields a cost-effectiveness ratio of $42 900 per life-year saved (95% CI, $21 200 to $71 300 per life-year saved) compared with cardiovascular-focused history and physical examination alone. Compared with no screening, ECG plus cardiovascular-focused history and physical examination saves 2.6 life-years per 1000 athletes screened and costs $199 per athlete, yielding a cost-effectiveness ratio of $76 100 per life-year saved ($62 400 to $130 000).Results are sensitive to the relative risk reduction associated with nonparticipation and the cost of initial screening.Effectiveness data are derived from 1 major European study. Patterns of causes of sudden death may vary among countries.Screening young athletes with 12-lead ECG plus cardiovascular-focused history and physical examination may be cost-effective.Stanford Cardiovascular Institute and the Breetwor Foundation.

Abstract

Obesity increases the risk of type 2 diabetes and coronary artery disease (CAD). Because all 3 conditions may reduce quality of life, the extent to which obesity, diabetes, and CAD independently affect quality of life is uncertain.Patients with type 2 diabetes and documented CAD participating in the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial at 45 clinical sites in the United States and Canada were studied in a cross-sectional analysis of baseline data. Quality of life was assessed with the Duke Activity Status Index, the energy/fatigue and health distress scales from the Medical Outcome Study, and overall self-rated health status.Higher body mass index was significantly associated with worse scores on all 4 quality of life scales, even after adjustment for the severity of diabetes and CAD and other comorbid conditions. Use of insulin, angina, and current smoking were also associated with significantly lower quality of life on all 4 scales, independent of other factors.Obesity is associated with significantly reduced quality of life in patients with diabetes and CAD, independent of comorbid conditions.

Abstract

Endothelium-derived nitric oxide plays a crucial role in the regulation of vascular tone and the development of cardiovascular disease. The endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) has emerged as a novel cardiovascular risk factor. ADMA appears to be an independent predictor for cardiovascular and overall mortality. However, the majority of studies investigating the clinical role of ADMA were performed in European study populations with few individuals of other ethnicities.We performed a cross-sectional study of 980 healthy, older (age 60-72 years) individuals of different ethnicities living in the San Francisco Bay area and analyzed ADMA plasma concentrations and their relationship to other cardiovascular risk factors. Plasma ADMA concentrations were measured using a recently developed, highly sensitive ELISA.In our entire sample, we were able to define a reference interval for ADMA plasma concentrations of 0.47 (90% CI 0.46-0.48) mumol/L to 0.85 (0.84-0.89) mumol/L. The mean ADMA concentration was 0.63 (SD 0.11) mumol/L (median 0.61 mumol/L). Mean ADMA concentrations were significantly lower in African Americans (0.60 mumol/L; P < 0.01) and mixed non-Hispanics (0.60 mumol/L; P < 0.05) compared with whites (0.63 mumol/L). ADMA was positively correlated with cystatin-C in both men (rho = 0.29) and women (rho = 0.37), and median plasma ADMA concentrations increased across cystatin-C quintiles.ADMA varies nearly 2-fold across a healthy sample of older men and women, correlates with age, body mass index, and renal function, and is different across ethnic groups. Additional studies in a wider age range and including larger ethnic subgroups would be useful.

Abstract

The goal of this study was to assess the rate and anatomical targets of repeat revascularization procedures in routine clinical practice after either bare-metal stent (BMS) or drug-eluting stent (DES) implantation. Randomized trials provide a reference standard for comparing outcomes after BMS or DES, but the rates of repeat revascularization procedures in clinical trials do not necessarily represent the rates in routine practice.Baseline and 1-year follow-up angiographic data from a cardiac catheterization laboratory data registry with 31 participating hospitals were analyzed.In 17 hospitals 14,459 eligible patients had a BMS implanted between 1998 and 2003, and in 20 hospitals 9,575 eligible patients had a DES implanted in 2005. DES patients had more multivessel disease and diabetes than BMS patients, but fewer DES patients had all diseased vessels stented. Over the subsequent year, there were significantly fewer repeat procedures in the initially stented region after DES than BMS (4.7% vs. 8.1%), but significantly more procedures in previously unstented remote segments (7.8% vs. 4.3%). Consequently, the overall rate of additional percutaneous coronary intervention admissions was not reduced by DES (12.5% vs. 12.3%; p > 0.7).In this sample of routine clinical practice DES reduced repeat intervention of the stented segment to a lesser extent than has been reported in randomized trials. For our cohort, the reduction in restenosis was offset by increased use of additional interventional procedures to treat remote segments, predominantly within the first 2 months after initial stenting.

Abstract

To design a multicenter study comparing the prognostic value and post-test resource utilization of PET, CT Coronary Angiography (CTA), and SPECT in clinical practice.Although PET, CTA, and SPECT are widely used, their relative clinical- and cost-effectiveness are undefined.The Study of Myocardial Perfusion and Coronary Anatomy Imaging Roles in CAD (SPARC) is a prospective, multicenter, observational registry that has enrolled 3019 patients undergoing clinically referred SPECT, PET, and CTA with the goal of comparing posttest resource utilization and comparative prognostic value. Resource utilization assessment will enroll intermediate-high likelihood patients without prior CAD, while prognostic assessment will include both these patients and patients with prior CAD. Secondary analyses include assessments of diagnostic accuracy, cost, and referral to revascularization. Sites recruited into at least two of the three imaging arms. Except for semi-quantitative interpretation, site protocols will be used for all imaging studies and images forwarded to an image repository. Follow-up for catheterization, revascularization, cardiac death, myocardial infarction, all-cause death and medication use changes will be performed at 90-day, 1, and 2 years. Standard statistical methods will be used to risk-adjust results within and between study arms. SPARC will have >85% power (two-sided test, alpha = 0.01) to detect a 5% catheterization rate difference at 90 days between the three arms and >90% power to detect a 2% difference in cardiac death, or nonfatal MI within 2 years of the index test.

Abstract

The field of outcomes research seeks to define optimal treatment in practice and to promote the rapid full adoption of efficacious therapies into routine clinical care. The American Heart Association (AHA) formed the AHA Pharmaceutical Roundtable (PRT) Outcomes Research Centers Network to accelerate attainment of these goals. Participating centers were intended to carry out state-of-the-art outcomes research in cardiovascular disease and stroke, to train the next generation of investigators, and to support the formation of a collaborative research network.After a competitive application process, 4 AHA PRT Outcomes Research Centers were selected: Duke Clinical Research Institute; Saint Luke's Mid America Heart Institute; Stanford University-Kaiser Permanente of Northern California; and University of California, Los Angeles. Each center proposed between 1 and 3 projects organized around a single theme in cardiovascular disease or stroke. Additionally, each center will select and train up to 6 postdoctoral fellows over the next 4 years, and will participate in cross-collaborative activities among the centers.The AHA PRT Outcomes Research Centers Network is designed to further strengthen the field of cardiovascular disease and stroke outcomes research by fostering innovative research, supporting high quality training, and encouraging center-to-center collaborations.

Abstract

Optimal treatment for patients with both type 2 diabetes mellitus and stable ischemic heart disease has not been established.We randomly assigned 2368 patients with both type 2 diabetes and heart disease to undergo either prompt revascularization with intensive medical therapy or intensive medical therapy alone and to undergo either insulin-sensitization or insulin-provision therapy. Primary end points were the rate of death and a composite of death, myocardial infarction, or stroke (major cardiovascular events). Randomization was stratified according to the choice of percutaneous coronary intervention (PCI) or coronary-artery bypass grafting (CABG) as the more appropriate intervention.At 5 years, rates of survival did not differ significantly between the revascularization group (88.3%) and the medical-therapy group (87.8%, P=0.97) or between the insulin-sensitization group (88.2%) and the insulin-provision group (87.9%, P=0.89). The rates of freedom from major cardiovascular events also did not differ significantly among the groups: 77.2% in the revascularization group and 75.9% in the medical-treatment group (P=0.70) and 77.7% in the insulin-sensitization group and 75.4% in the insulin-provision group (P=0.13). In the PCI stratum, there was no significant difference in primary end points between the revascularization group and the medical-therapy group. In the CABG stratum, the rate of major cardiovascular events was significantly lower in the revascularization group (22.4%) than in the medical-therapy group (30.5%, P=0.01; P=0.002 for interaction between stratum and study group). Adverse events and serious adverse events were generally similar among the groups, although severe hypoglycemia was more frequent in the insulin-provision group (9.2%) than in the insulin-sensitization group (5.9%, P=0.003).Overall, there was no significant difference in the rates of death and major cardiovascular events between patients undergoing prompt revascularization and those undergoing medical therapy or between strategies of insulin sensitization and insulin provision. (ClinicalTrials.gov number, NCT00006305.)

Abstract

Anemia management remains complicated in patients with endstage renal disease on hemodialysis. We wished to evaluate the effect of protocol adherence to EPO and intravenous iron dosing on achieving the desired range of hemoglobin levels.A cohort of hemodialysis patients was studied to evaluate the rate of adherence to EPO and iron dosing protocols over a 5 month period. A database was completed to evaluate all known comorbidities, demographic factors, and facility issues that might affect hemoglobin levels. A logistic regression model was employed to evaluate the effect of adherence to the anemia protocols on the probability of achieving a hemoglobin level below, within or above the targeted range of 11-12.5 g/dl.Among 2114 patients, we found that adherence to both the EPO and iron dosing protocol resulted in the greatest probability of achieving the target hemoglobin range (56 +/- 5% in anemia protocol adherent patients versus 42 +/- 7% in non adherent patients). This was predominantly due to a lowered risk of having above target hemoglobin levels rather than below. The use of the anemia protocols was associated with lower rates of hospitalization (9 +/- 0.7 visits/100 months in adherent group vs 15 +/- 2 in non adherent group) and lower utilization of both EPO and intravenous iron. Furthermore, patients in the adherent groups had less variability of their hemoglobin levels month by month, at least as judged by standard deviation.Adherence to anemia protocols, as practiced in the dialysis units included in this cohort, may improve hemodialysis patients' ability to achieve target hemoglobin levels, and by avoiding above target hemoglobin values, lower drug utilization and reduce variability of hemoglobin levels.

Abstract

Change in coronary artery calcification is a surrogate marker of subclinical coronary artery disease (CAD). In the only large prospective study, CAD risk factors predicted progression of coronary artery calcium (CAC).We measured CAC at enrollment and after 24 months in a community-based sample of 869 healthy adults aged 60 to 72 years who were free of clinical CAD. We assessed predictors of the progression of CAC using univariate and multivariate models after square root transformation of the Agatston scores. Predictors tested included age, sex, race/ethnicity, smoking status, body mass index, family history of CAD, C-reactive protein and several measures of diabetes, insulin levels, blood pressure, and lipids.The mean age of the cohort was 66 years, and 62% were male. The median CAC at entry was 38.6 Agatston units and increased to 53.3 Agatston units over 24 months (P < .01). The CAC progression was associated with white race, diabetes, dyslipidemia, hypertension, lower diastolic blood pressure, and higher pulse pressure. After controlling for these variables, higher fasting insulin levels independently predicted CAC progression.Insulin resistance, in addition to the traditional cardiac risk factors, independently predicts progression of CAC in a community-based population without clinical CAD.

Abstract

In observational studies, clinical outcomes for black patients with coronary disease have been worse than for white patients. There are few data from randomized trials comparing the outcomes of coronary revascularization between black patients and white patients.We analyzed data from the Bypass Angioplasty Revascularization Investigation randomized trial. At study entry, the 113 black patients had significantly higher rates of diabetes, hypertension, smoking, heart failure, and abnormal left ventricular function than the 1653 white patients. Black patients had significantly higher mortality than white patients (hazard ratio, 2.16; P<0.001), which remained significant after statistical adjustment for differences in baseline clinical characteristics (hazard ratio, 1.59; P=0.003). In a substudy of economic and quality of life outcomes, the 67 black patients had similar frequency of physician visits and use of evidence-based cardiac medications but significantly worse physical function scores than the 885 white patients. The effect of random assignment to either surgery or angioplasty on clinical outcomes was not significantly modified by race (interaction probability values >or=0.18).Clinical outcomes of black patients after coronary revascularization were worse than those of white patients in a clinical trial setting with similar treatment and access to care. The differences in outcome between black and white patients were not completely attributable to the greater levels of comorbidity among black patients at study entry.

Abstract

Statins reduce the rates of heart attacks, strokes, and revascularization procedures (ie, major vascular events) in a wide range of circumstances. Randomized controlled trial data from 20,536 adults have been used to estimate the cost-effectiveness of prescribing statin therapy in the United States for people at different levels of vascular disease risk and to explore whether wider use of generic statins beyond the populations currently recommended for treatment in clinical guidelines is indicated.Randomized controlled trial data, an internally validated vascular disease model, and US costs of statin therapy and other medical care were used to project lifetime risks of vascular events and evaluate the cost-effectiveness of 40 mg simvastatin daily. For an average of 5 years, allocation to simvastatin reduced the estimated US costs of hospitalizations for vascular events by approximately 20% (95% CI, 15 to 24) in the different subcategories of participants studied. At a daily cost of $1 for 40 mg generic simvastatin, the estimated costs of preventing a vascular death within the 5-year study period ranged from a net saving of $1300 (95% CI, $15,600 saving to $13,200 cost) among participants with a 42% 5-year major vascular event risk to a net cost of $216,500 ($123,700 to $460,000 cost) among those with a 12% 5-year risk. The costs per life year gained with lifetime simvastatin treatment ranged from $2500 (-$40 to $3820) in people aged 40 to 49 years with a 42% 5-year major vascular event risk to $10,990 ($9430 to $14,700) in people aged 70 years and older with a 12% 5-year risk.Treatment with generic simvastatin appears to be cost-effective for a much wider population in the United States than that recommended by current guidelines.

Abstract

Accurate, high-throughput genotyping allows the fine characterization of genetic ancestry. Here we applied recently developed statistical and computational techniques to the question of African ancestry in African Americans by using data on more than 450,000 single-nucleotide polymorphisms (SNPs) genotyped in 94 Africans of diverse geographic origins included in the HGDP, as well as 136 African Americans and 38 European Americans participating in the Atherosclerotic Disease Vascular Function and Genetic Epidemiology (ADVANCE) study. To focus on African ancestry, we reduced the data to include only those genotypes in each African American determined statistically to be African in origin.From cluster analysis, we found that all the African Americans are admixed in their African components of ancestry, with the majority contributions being from West and West-Central Africa, and only modest variation in these African-ancestry proportions among individuals. Furthermore, by principal components analysis, we found little evidence of genetic structure within the African component of ancestry in African Americans.These results are consistent with historic mating patterns among African Americans that are largely uncorrelated to African ancestral origins, and they cast doubt on the general utility of mtDNA or Y-chromosome markers alone to delineate the full African ancestry of African Americans. Our results also indicate that the genetic architecture of African Americans is distinct from that of Africans, and that the greatest source of potential genetic stratification bias in case-control studies of African Americans derives from the proportion of European ancestry.

Abstract

Single nucleotide polymorphisms (SNPs) in the peroxisome proliferator-activated receptor gamma (PPARG) gene have been associated with cardiovascular risk factors, particularly obesity and diabetes. We assessed the relationship between 4 PPARG SNPs (C-681G, C-689T, Pro12Ala, and C1431T) and coronary heart disease (CHD) in the PRIME (249 cases/494 controls, only men) and ADVANCE (1,076 cases/805 controls, men or women) studies. In PRIME, homozygote individuals for the minor allele of the PPARG C-689T, Pro12Ala, and C1431T SNPs tended to have a higher risk of CHD than homozygote individuals for the frequent allele (adjusted OR [95% CI] = 3.43 [0.96-12.27], P = .058, 3.41 [0.95-12.22], P = .060 and 5.10 [0.99-26.37], P = .050, resp.). No such association could be detected in ADVANCE. Haplotype distributions were similar in cases and control in both studies. A meta-analysis on the Pro12Ala SNP, based on our data and 11 other published association studies (6,898 CHD cases/11,287 controls), revealed that there was no evidence for a significant association under the dominant model (OR = 0.99 [0.92-1.07], P = .82). However, there was a borderline association under the recessive model (OR = 1.29 [0.99-1.67], P = .06) that became significant when considering men only (OR = 1.73 [1.20-2.48], P = .003). In conclusion, the PPARG Ala12Ala genotype might be associated with a higher CHD risk in men but further confirmation studies are needed.

Abstract

Small asymptomatic lung nodules are found frequently in the course of cardiac computed tomography (CT) scanning. However, the utility of assessing and reporting incidental findings in healthy, asymptomatic subjects is unknown.The sample comprised 1023 60- to 69-year-old subjects free of clinical cardiovascular disease and cancer who participated in the Atherosclerotic Disease, VAscular functioN and genetiC Epidemiology Study. All subjects underwent cardiac CT for determination of coronary calcium between 2001 and 2004, and the first 459 subjects were assessed for incidental pulmonary findings. We used health plan clinical databases to ascertain 24-month health care use and clinical outcomes.Noncalcified pulmonary nodules were reported in 81 of 459 subjects (18%). Chest CT was performed on 78% of participants in the 24 months after notification, compared with 2.5% in the previous 24 months. Chest x-ray use increased from 28% to 49%. The mean number of chest CT scans per subject was 1.3 (range, 0-5). Although no malignant lesions were diagnosed in the group who had pulmonary findings read, 1 lung cancer case was diagnosed in the group who did not have lung findings read. Among the 63 participants followed up by CT, the original lesion was not identified in 22 participants (35%), the lesion had decreased or remained stable in 39 participants (62%), and there was interval growth in 2 participants (3%).Reporting noncalcified pulmonary nodules resulted in substantial rescanning that overwhelmingly revealed resolution or stability of pulmonary nodules, arguing for benign processes.

Abstract

This study sought to systematically compare the effectiveness of percutaneous coronary intervention and coronary artery bypass surgery in patients with single-vessel disease of the proximal left anterior descending (LAD) coronary artery.It is uncertain whether percutaneous coronary interventions (PCI) or coronary artery bypass grafting (CABG) surgery provides better clinical outcomes among patients with single-vessel disease of the proximal LAD.We searched relevant databases (MEDLINE, EMBASE, and Cochrane from 1966 to 2006) to identify randomized controlled trials that compared outcomes for patients with single-vessel proximal LAD assigned to either PCI or CABG.We identified 9 randomized controlled trials that enrolled a total of 1,210 patients (633 received PCI and 577 received CABG). There were no differences in survival at 30 days, 1 year, or 5 years, nor were there differences in the rates of procedural strokes or myocardial infarctions, whereas the rate of repeat revascularization was significantly less after CABG than after PCI (at 1 year: 7.3% vs. 19.5%; at 5 years: 7.3% vs. 33.5%). Angina relief was significantly greater after CABG than after PCI (at 1 year: 95.5% vs. 84.6%; at 5 years: 84.2% vs. 75.6%). Patients undergoing CABG spent 3.2 more days in the hospital than those receiving PCI (95% confidence interval: 2.3 to 4.1 days, p < 0.0001), required more transfusions, and were more likely to have arrhythmias immediately post-procedure.In patients with single-vessel, proximal LAD disease, survival was similar in CABG-assigned and PCI-assigned patients; CABG was significantly more effective in relieving angina and led to fewer repeat revascularizations.

Abstract

To describe the impact of coronary artery bypass graft (CABG) surgery on health related quality of life (HRQOL) in post-menopausal women.Prospective cohort study.Women enrolled in the Heart and Estrogen/progestin Replacement Study (HERS).One hundred and thirty-seven women (mean age 66.6) who had CABG surgery while enrolled in HERS.Physical function was assessed using the 12-item Duke Activity Status Index (DASI), energy-fatigue with the four-item RAND scale, and mental health with the RAND mental health inventory each year. We defined baseline HRQOL from the interview that preceded the CABG (mean 4.6 months pre-CABG). To assess post-CABG HRQOL, we used the first interview that was obtained at least 6 months following the CABG (mean 11.5 months post-CABG).For all three measures of HRQOL, mean scores post-CABG were virtually identical to mean scores pre-CABG (mean pre and post scores were 20.8, 20.4 for physical function, 49.3, 49.2 for energy-fatigue, and 71.9 and 72.3 for mental health). After adjusting for demographic and clinical characteristics and the expected temporal change in HRQOL, differences between pre and post-operative HRQOL remained minimal. However, on an individual patient level, there was significant variability in HRQOL outcomes. For example, while mean physical function scores changed little, 32% of women were at least moderately better (scores improved by at least 0.5 standard deviations) following surgery, while 26% were at least moderately worse (scores declined by at least 0.5 standard deviations).Following CABG surgery in post-menopausal women, on average, HRQOL is virtually identical to the pre-operative baseline. However, there is significant variability, as substantial numbers of women are significantly better or significantly worse.

Abstract

A susceptibility locus for coronary artery disease (CAD) at chromosome 9p21 has recently been reported, which may influence the age of onset of CAD. We sought to replicate these findings among white subjects and to examine whether these results are consistent with other racial/ethnic groups by genotyping three single nucleotide polymorphisms (SNPs) in the risk interval in the Atherosclerotic Disease, Vascular Function, and Genetic Epidemiology (ADVANCE) study. One or more of these SNPs was associated with clinical CAD in whites, U.S. Hispanics and U.S. East Asians. None of the SNPs were associated with CAD in African Americans although the power to detect an odds ratio (OR) in this group equivalent to that seen in whites was only 24-30%. ORs were higher in Hispanics and East Asians and lower in African Americans, but in all groups the 95% confidence intervals overlapped with ORs observed in whites. High-risk alleles were also associated with increased coronary artery calcification in controls and the magnitude of these associations by racial/ethnic group closely mirrored the magnitude observed for clinical CAD. Unexpectedly, we noted significant genotype frequency differences between male and female cases (P = 0.003-0.05). Consequently, men tended towards a recessive and women tended towards a dominant mode of inheritance. Finally, an effect of genotype on the age of onset of CAD was detected but only in men carrying two versus one or no copy of the high-risk allele and presenting with CAD at age >50 years. Further investigations in other populations are needed to confirm or refute our findings.

Abstract

Murine genetic models suggest that function of the 12/15-LOX enzyme promotes atherosclerosis. We tested the hypothesis that exonic and/or promoter single nucleotide polymorphisms (SNPs) in the human 12/15-LOX gene (ALOX15) alter the risk of symptomatic coronary artery disease (CAD).We resequenced ALOX15 and then genotyped a common promoter and a less common novel coding SNP (T560M) in 1809 subjects with CAD and 1734 controls from Kaiser Permanente including a subset of participants of the Coronary Artery Risk Development in Young Adults study. We found no association between the promoter SNP and the risk of CAD. However, heterozygote carriers of the 560M allele had an increased risk of CAD (adjusted OR, 1.62; P=0.02) compared to non-carriers. In vitro studies demonstrated a 20-fold reduction in the catalytic activity of 560M when compared to 560T. We then genotyped T560M in 12,974 participants of the Atherosclerosis Risk in Communities study and similarly found that heterozygote carriers had an increased risk of CAD compared to non-carriers (adjusted HR, 1.31; P=0.06). In both population studies, homozygote carriers were rare and associated with a non-significant decreased risk of CAD compared to non-carriers (adjusted OR, 0.55; P=0.63 and HR, 0.93; P=0.9).A coding SNP in ALOX15 (T560M) results in a near null variant of human 12/15-LOX. Assuming a co-dominant mode of inheritance, this variant does not protect against CAD. Assuming a recessive mode of inheritance, the effect of this mutation remains unclear, but is unlikely to provide a protective effect to the degree suggested by mouse knockout studies.

Abstract

Recent human genetic studies suggest that allelic variants of leukotriene pathway genes influence the risk of clinical and subclinical atherosclerosis. We sequenced the promoter, exonic, and splice site regions of ALOX5 and ALOX5AP and then genotyped 7 SNPs in ALOX5 and 6 SNPs in ALOX5AP in 1,552 cases with clinically significant coronary artery disease (CAD) and 1,583 controls from Kaiser Permanente including a subset of participants of the coronary artery risk development in young adults study. A nominally significant association was detected between a promoter SNP in ALOX5 (rs12762303) and CAD in our subset of white/European subjects (adjusted odds ratio per minor allele, log-additive model, 1.32; P = 0.002). In this race/ethnic group, rs12762303 has a minor allele frequency of 15% and is tightly linked to variation at the SP1 variable tandem repeat promoter polymorphism. However, the association between CAD and rs12762303 could not be reproduced in the atherosclerosis risk in communities study (hazard rate ratio per minor allele; 1.08, P = 0.1). Assuming a recessive mode of inheritance, the association was not significant in either population study but our power to detect modest effects was limited. No significant associations were observed between all other SNPs and the risk of CAD. Overall, our findings do not support a link between common allelic variation in or near ALOX5 or ALOX5AP and the risk of CAD. However, additional studies are needed to exclude modest effects of promoter variation in ALOX5 on the risk of CAD assuming a recessive mode of inheritance.

Abstract

With the widespread use of cardiac multidetector row computed tomography (MDCT), the issue of incidental findings is receiving increasing attention. Our objectives were to evaluate the prevalence of incidental findings discovered during cardiac MDCT scanning and to identify clinical variables associated with incidental findings.This cross-sectional analysis involved a population-based sample recruited from an integrated health care delivery system in Northern California as part of the Atherosclerotic Disease, Vascular Function and Genetic Epidemiology (ADVANCE) Study. Healthy men and women aged 60 to 69 years without diagnosed cardiovascular disease underwent cardiac MDCT for the detection and quantification of coronary artery calcification. The images were prospectively evaluated for incidental findings.A total of 459 participants underwent MDCT scanning, and the overall prevalence of any incidental finding was 41%. Of the 459 participants, 105 (23%) had at least 1 incidental finding that was recommended for clinical or radiological follow-up examination, the most common of which was single or multiple pulmonary nodules (18%). Participants with and without incidental findings had comparable baseline demographics and selected clinical variables, although there were significantly fewer men and a significantly lower prevalence of the metabolic syndrome in those with incidental findings.Incidental findings, especially pulmonary nodules, are common in cardiac MDCT performed to assess coronary artery calcification in older healthy adults. The net risks and benefits of looking for noncardiac abnormalities during cardiac MDCT should be rigorously evaluated.

Abstract

The lectin-like oxidized LDL receptor LOX-1 (encoded by OLR1) is believed to play a key role in atherogenesis and some reports suggest an association of OLR1 polymorphisms with myocardial infarction (MI). We tested whether single nucleotide polymorphisms (SNPs) in OLR1 are associated with clinically significant CAD in the Atherosclerotic Disease, VAscular FuNction, & Geneti C Epidemiology (ADVANCE) study.ADVANCE is a population-based case-control study of subjects receiving care within Kaiser Permanente of Northern California including a subset of participants of the Coronary Artery Risk Development in Young Adults (CARDIA) study. We first resequenced the promoter, exonic, and splice site regions of OLR1 and then genotyped four single nucleotide polymorphisms (SNPs), including a non-synonymous SNP (rs11053646, Lys167Asn) as well as an intronic SNP (rs3736232) previously associated with CAD.In 1,809 cases with clinical CAD and 1,734 controls, the minor allele of the coding SNP was nominally associated with a lower odds ratio (OR) of CAD across all ethnic groups studied (minimally adjusted OR 0.8, P = 0.007; fully adjusted OR 0.8, P = 0.01). The intronic SNP was nominally associated with an increased risk of CAD (minimally adjusted OR 1.12, p = 0.03; fully adjusted OR 1.13, P = 0.03). However, these associations were not replicated in over 13,200 individuals (including 1,470 cases) in the Atherosclerosis Risk in Communities (ARIC) study.Our results do not support the presence of an association between selected common SNPs in OLR1 and the risk of clinical CAD.

Abstract

The aim of this study was to assess systematic differences between patients with acute myocardial infarction (MI) and patients with stable angina in matrix metalloproteinase (MMP) circulating levels and genetic polymorphisms.We identified adults in a large integrated health care delivery system whose initial clinical presentation of coronary disease was either an acute MI or stable exertional angina. A total of 909 patients with acute MI, 466 patients with stable angina, and 1023 healthy older control subjects were genotyped. Serum levels of pro-MMP1, MMP2, MMP3, MMP9, and MMP10 were measured in 199 randomly selected patients from each group.At a median of 15 weeks after initial clinical presentation, higher circulating levels of MMP2 and MMP9 were independently associated with acute MI after statistical adjustment for conventional risk factors, hs-CRP levels, and cardiac medications. By contrast, none of the polymorphisms in MMP1, MMP2, MMP3, MMP9, or MMP10 was significantly associated with either acute MI compared with angina, or with coronary disease compared with controls.Circulating levels of MMP2 and MMP9 are independently associated with development of an acute MI rather than stable angina as the initial clinical presentation of coronary artery disease.

Abstract

Genetic polymorphisms may affect the balance between coagulation and fibrinolysis and thereby affect individual vulnerability to acute myocardial infarction (MI) among patients with underlying coronary atherosclerosis.We enrolled 1375 patients with an initial clinical presentation of coronary disease. We genotyped 49 single nucleotide polymorphisms (SNPs) in 9 coagulation system genes and compared patients who had an initial acute MI with patients who presented with stable exertional angina.An SNP in CD36 (rs3211956) was significantly (P = .04) more common among patients who presented with acute MI (minor allele frequency 10.5%) than patients with stable exertional angina (minor allele frequency 8.0%). This association became marginally significant, however, after adjustment for conventional cardiac risk factors in an additive genetic model (odds ratio 1.34, CI 1.00-1.88, P = .053). An SNP in ITGB3 (Leu59Pro, rs5918) was slightly, but not significantly (P = .083), more common among patients with acute MI (minor allele frequency 14.5%) than among patients with stable exertional angina (minor allele frequency 12.0%). Two linked SNPs in THBD (Ala473Val, rs1042579; and rs3176123) were slightly, but not significantly (P = .079 and 0.052, respectively), less common among patients with acute MI (minor allele frequency 16.1%) than among patients with stable exertional angina (18.7% and 19.0%, respectively).Four SNPs in platelet glycoprotein and hemostatic genes were nominally associated with acute MI rather than stable exertional angina as the initial clinical presentation of coronary artery disease. These findings are suggestive but require independent confirmation in larger studies.

Abstract

Circulating concentrations of proteins associated with coagulation and fibrinolysis may differ between individuals with coronary artery disease (CAD) who develop an acute myocardial infarction (AMI) rather than stable exertional angina.We compared plasma concentrations of fibrinogen, d-dimer, tissue-type plasminogen activator, and plasminogen activator inhibitor-1 (PAI-1) between patients whose first clinical manifestation of CAD was an AMI (n = 198) rather than stable exertional angina (n = 199). We also compared plasma concentrations of these proteins between patients with symptomatic CAD (either AMI or stable angina; n = 397) and healthy, control subjects (n = 197) to confirm the sensitivity of these assays to detect epidemiologic associations.At a median of 15 weeks after presentation, patients with AMI had slightly higher d-dimer concentrations than patients with stable angina (P = .057), but were not significantly different in other markers. By contrast, fibrinogen, d-dimer, and tissue-type plasminogen activator were significantly higher (P < .001) and PAI-1 lower in patients with CAD than in healthy control subjects. After statistical adjustment for clinical covariates, cardiac risk factors, medications, and other confounders, fibrinogen, d-dimer, and PAI-1 remained significantly associated with CAD.Selected plasma markers of coagulation and fibrinolysis did not distinguish patients presenting with AMI from those with stable exertional angina.

Abstract

Only some patients with coronary artery disease (CAD) develop acute myocardial infarction (MI), and emerging evidence suggests vulnerability to MI varies systematically among patients and may have a genetic component. The goal of this study was to assess whether polymorphisms in genes encoding elements of pathways mediating the response to ischemia affect vulnerability to MI among patients with underlying CAD.We prospectively identified patients at the time of their initial clinical presentation of CAD who had either an acute MI or stable exertional angina. We collected clinical data and genotyped 34 polymorphisms in 6 genes (ANGPT1, HIF1A, THBS1, VEGFA, VEGFC, VEGFR2).The 909 patients with acute MI were significantly more likely than the 466 patients with stable angina to be male, current smokers, and hypertensive, and less likely to be taking beta-blockers or statins. Three polymorphisms in HIF1A (Pro582Ser, rs11549465; rs1087314; and Thr418Ile, rs41508050) were significantly more common in patients who presented with stable exertional angina rather than acute MI, even after statistical adjustment for cardiac risk factors and medications. The HIF-mediated transcriptional activity was significantly lower when HIF1A null fibroblasts were transfected with variant HIF1A alleles than with wild-type HIF1A alleles.Polymorphisms in HIF1A were associated with development of stable exertional angina rather than acute MI as the initial clinical presentation of CAD.

Abstract

The comparative effectiveness of coronary artery bypass graft (CABG) surgery and percutaneous coronary intervention (PCI) for patients in whom both procedures are feasible remains poorly understood.To compare the effectiveness of PCI and CABG in patients for whom coronary revascularization is clinically indicated.MEDLINE, EMBASE, and Cochrane databases (1966-2006); conference proceedings; and bibliographies of retrieved articles.Randomized, controlled trials (RCTs) reported in any language that compared clinical outcomes of PCI with those of CABG, and selected observational studies.Information was extracted on study design, sample characteristics, interventions, and clinical outcomes.The authors identified 23 RCTs in which 5019 patients were randomly assigned to PCI and 4944 patients were randomly assigned to CABG. The difference in survival after PCI or CABG was less than 1% over 10 years of follow-up. Survival did not differ between PCI and CABG for patients with diabetes in the 6 trials that reported on this subgroup. Procedure-related strokes were more common after CABG than after PCI (1.2% vs. 0.6%; risk difference, 0.6%; P = 0.002). Angina relief was greater after CABG than after PCI, with risk differences ranging from 5% to 8% at 1 to 5 years (P < 0.001). The absolute rates of angina relief at 5 years were 79% after PCI and 84% after CABG. Repeated revascularization was more common after PCI than after CABG (risk difference, 24% at 1 year and 33% at 5 years; P < 0.001); the absolute rates at 5 years were 46.1% after balloon angioplasty, 40.1% after PCI with stents, and 9.8% after CABG. In the observational studies, the CABG-PCI hazard ratio for death favored PCI among patients with the least severe disease and CABG among those with the most severe disease.The RCTs were conducted in leading centers in selected patients. The authors could not assess whether comparative outcomes vary according to clinical factors, such as extent of coronary disease, ejection fraction, or previous procedures. Only 1 small trial used drug-eluting stents.Compared with PCI, CABG was more effective in relieving angina and led to fewer repeated revascularizations but had a higher risk for procedural stroke. Survival to 10 years was similar for both procedures.

Abstract

Serum inflammatory markers correlate with outcome and response to therapy in subjects with cardiovascular disease. However, current individual markers lack specificity for the diagnosis of coronary artery disease (CAD). We hypothesize that a multimarker proteomic approach measuring serum levels of vascular derived inflammatory biomarkers could reveal a "signature of disease" that can serve as a highly accurate method to assess for the presence of coronary atherosclerosis. We simultaneously measured serum levels of seven chemokines [CXCL10 (IP-10), CCL11 (eotaxin), CCL3 (MIP1 alpha), CCL2 (MCP1), CCL8 (MCP2), CCL7 (MCP3), and CCL13 (MCP4)] in 48 subjects with clinically significant CAD ("cases") and 44 controls from the ADVANCE Study. We applied three classification algorithms to identify the combination of variables that would best predict case-control status and assessed the diagnostic performance of these models with receiver operating characteristic (ROC) curves. The serum levels of six chemokines were significantly higher in cases compared with controls (P < 0.05). All three classification algorithms entered three chemokines in their final model, and only logistic regression selected clinical variables. Logistic regression produced the highest ROC of the three algorithms (AUC = 0.95; SE = 0.03), which was markedly better than the AUC for the logistic regression model of traditional risk factors of CAD without (AUC = 0.67; SE = 0.06) or with CRP (AUC = 0.68; SE = 0.06). A combination of serum levels of multiple chemokines identifies subjects with clinically significant atherosclerotic heart disease with a very high degree of accuracy. These results need to be replicated in larger cross-sectional studies and their prognostic value explored.

Abstract

Measurement of coronary artery calcium (CAC) has been proposed as a screening tool, but CAC levels may differ according to race and gender. Racial/ethnic and gender distributions of CAC were examined in a randomly selected cohort of 60- to 69-year-old healthy subjects. Demographic, race/ethnicity (R/E), and clinical characteristics and assessment of CAC were collected. There were 723 white/European, 105 African-American, 73 Hispanic, and 67 East Asian subjects (597 men, 369 women) included in this analysis. Men had a significantly higher prevalence of any CAC (score>10) than women (76% vs 41%; p<0.0001). For men, the unadjusted odds of having any CAC was 2.2 (95% confidence interval [CI] 1.3 to 3.8) for whites compared with African-Americans. For women, CAC scores were not significantly different across ethnic groups. After adjustment for coronary risk factors, African-American and East Asian R/E remained associated with a lower prevalence of CAC in men (adjusted odds ratios [ORs] 0.33 and 0.47, respectively), as well as older age (OR 1.2, 95% CI 1.1 to 1.3), known hyperlipidemia (OR 1.7, 95% CI 1.1 to 2.7), and history of hypertension (OR 2.2, 95% CI 1.4 to 3.3). In women, Asian R/E (OR 2.5, 95% CI 1.1 to 5.7), history of smoking (adjusted OR 2.8, 95% CI 1.3 to 6.1), and known hyperlipidemia (adjusted OR 2.0, 95% CI 1.3 to 3.1) were associated with a higher prevalence of CAC independent of other risk factors. In conclusion, our data indicate that the presence of CAC varied significantly across selected race/ethnic groups independent of traditional cardiovascular risk factors.

Abstract

To determine the utility of the Stanford Brief Activity Survey (SBAS) as a quick screening tool in a clinical population, where no other measure of physical activity was available.The SBAS was administered to 500 younger cases in the Atherosclerotic Disease Vascular Function and Genetic Epidemiology (ADVANCE) study, a case-control genetic association study, between December 2001 and January 2004. Younger cases in the ADVANCE study included men (<46 years old) and women (<56 years old) diagnosed with early-onset coronary artery disease. Frequency distributions of the SBAS and associations between SBAS activity categories and selected cardiovascular disease risk factors by sex were calculated.Subjects were 45.9 +/- 6.4 years old, 68% married, 61% women, 51% white, and 21% college graduates. Clinical diagnoses for early-onset coronary artery disease included 61% myocardial infarction, 23% coronary revascularization procedure, and 16% angina pectoris. In women, associations between all cardiovascular disease risk factors examined across SBAS categories were statistically significant (P trend < .01). In men, the associations across SBAS categories were statistically significant (P trend < .01), except for body mass index (P trend = .065). Adjustment for body mass index, age, ethnicity, and education with interactions by sex did not change the results.Subjects in the higher SBAS activity categories had more favorable cardiovascular disease risk profiles than did their less active counterparts, regardless of sex. The SBAS can be recommended for use in clinical populations providing immediate feedback on current physical activity level.

Abstract

Although current evidence supporting a more precise strategy for identifying patients at highest risk for sudden cardiac death (SCD) is sparse, strategies for translating existing and future evidence into clinical practice and policy are needed today. A great many unanswered questions exist. Examples include the following: At what level of risk for SCD should we pursue further testing or therapy? How should clinical strategies ethically and economically balance alternative outcomes? How can we best translate optimal strategies into clinical practice so as to prevent tomorrow's SCDs? On July 20 and 21, 2006, a group of individuals with expertise in clinical cardiovascular medicine, biostatistics, economics, and health policy was joined by government (Food and Drug Administration; Centers for Medicare and Medicaid Services; National Heart, Lung, and Blood Institute; Agency for Healthcare Research and Quality), professional societies (Heart Rhythm Society), and industry to discuss strategies for risk assessment and prevention of SCD. The meeting was organized by the Duke Center for the Prevention of Sudden Cardiac Death and the Duke Clinical Research Institute. This article, the second of 2 documents, summarizes the policy discussions of that meeting, discusses an analytic framework for evaluating the risks and benefits associated with SCD prevention and risk stratification, and addresses the translation of SCD risk assessment strategies into practice and policy.

Abstract

Accurate and timely prediction of sudden cardiac death (SCD) is a necessary prerequisite for effective prevention and therapy. Although the largest number of SCD events occurs in patients without overt heart disease, there are currently no tests that are of proven predictive value in this population. Efforts in risk stratification for SCD have focused primarily on predicting SCD in patients with known structural heart disease. Despite the ubiquity of tests that have been purported to predict SCD vulnerability in such patients, there is little consensus on which test, in addition to the left ventricular ejection fraction, should be used to determine which patients will benefit from an implantable cardioverter defibrillator. On July 20 and 21, 2006, a group of experts representing clinical cardiology, cardiac electrophysiology, biostatistics, economics, and health policy were joined by representatives of the US Food and Drug administration, Centers for Medicare Services, Agency for Health Research and Quality, the Heart Rhythm Society, and the device and pharmaceutical industry for a round table meeting to review current data on strategies of risk stratification for SCD, to explore methods to translate these strategies into practice and policy, and to identify areas that need to be addressed by future research studies. The meeting was organized by the Duke Center for the Prevention of SCD at the Duke Clinical Research Institute and was funded by industry participants. This article summarizes the presentations and discussions that occurred at that meeting.

Abstract

We sought to compare 10-year clinical outcomes in the BARI (Bypass Angioplasty Revascularization Investigation) trial patients who were randomly assigned to percutaneous transluminal coronary balloon angioplasty (PTCA) versus coronary artery bypass grafting (CABG).Angioplasty and bypass surgery have been compared in numerous studies, but long-term clinical outcomes are limited.Symptomatic patients with multivessel coronary artery disease (n = 1,829) were randomly assigned to initial treatment with PTCA or CABG and followed up for an average of 10.4 years. Analyses were conducted on an intention-to-treat basis.The 10-year survival was 71.0% for PTCA and 73.5% for CABG (p = 0.18). At 10 years, the PTCA group had substantially higher subsequent revascularization rates than the CABG group (76.8% vs. 20.3%, p < 0.001), but angina rates for the 2 groups were similar. In the subgroup of patients with no treated diabetes, survival rates were nearly identical by randomization (PTCA 77.0% vs. CABG 77.3%, p = 0.59). In the subgroup with treated diabetes, the CABG assigned group had higher survival than the PTCA assigned group (PTCA 45.5% vs. CABG 57.8%, p = 0.025).There was no significant long-term disadvantage regarding mortality or myocardial infarction associated with an initial strategy of PTCA compared with CABG. Among patients with treated diabetes, CABG conferred long-term survival benefit, whereas the 2 initial strategies were equivalent regarding survival for patients without diabetes.

Abstract

Increased use of ICDs in patients with cardiac disease has the potential to strain national health care budgets because of the large numbers of eligible patients and the high cost of the ICDs. Randomized trials show ICDs increase life-expectancy in some groups of patients and also increase total medical costs significantly. ICDs exemplify the role of new technology as the main force behind rising health care costs. ICDs have not been used in all eligible patients, in part because of cost, but also because of patient resistance and a shortage of specialists able to implant and manage complex ICDs. The cost-effectiveness of ICDs would be improved by development of simpler and cheaper devices, and by better tools to identify patients who benefit from an ICD.

Abstract

Leptin is associated with adiposity and insulin resistance and may play a direct role in vascular calcification. It is unclear, however, whether leptin is an independent predictor of atherosclerotic burden.The aim of this study was to examine the association between plasma leptin and coronary artery calcification (CAC) in an ethnically diverse cohort of older adult men and women free of clinical cardiovascular disease.This was a cross-sectional study with data collection between January 2002 and February 2004 as part of the ADVANCE Study.The study was conducted at an integrated health care delivery system in Northern California.Participants included 949 men and women aged 60-69 yr old.There were no interventions.The main outcome measure was CAC by multidetector row computed tomography.In ordinal logistic regression, plasma leptin levels were positively associated with extent of CAC independently of age, race/ethnicity, and smoking status in women (odds ratio of higher CAC for the sex-specific upper tertile vs. lower tertile = 1.81; 95% confidence interval, 1.10-3.00) but not in men (odds ratio = 1.29; 95% confidence interval = 0.89-1.86). However, this association was explained by metabolic risk factors and adiposity measures.Our findings support a role of leptin on vascular calcification in women but, in our sample of older adults, the association between leptin and CAC was not independent of other cardiac risk factors.

Abstract

We sought to examine the association between the metabolic syndrome (MetS) (defined both by the 2001 National Cholesterol Educational Program Adult Treatment Panel III [ATP-III] definition and the American Heart Association/National Heart, Lung and Blood Institute [AHA/NHLBI] revision incorporating the lower threshold for impaired fasting glucose [IFG]) and early-onset coronary artery disease (CAD).The impact of MetS on premature CAD has not been studied extensively. Lowering the threshold to define the IFG component (from 110 to 100 mg/dl) and the value of the syndrome as a whole versus its individual components are subjects of intense debate.We performed a case-control study with 393 early-onset CAD subjects (acute myocardial infarction, angina with > or =50% stenosis, or coronary revascularization) in men under age 46 years or women under age 56 years and 393 control subjects individually matched for gender, age, and race/ethnicity.By conditional logistic regression, presence of ATP-III MetS without diabetes (adjusted odds ratio [adj-OR] 4.9; 95% confidence interval [CI] 3.4 to 8.0) and with diabetes (adj-OR 8.0, 95% CI 4.39 to 14.6) was a strong independent determinant of early-onset CAD. Using the AHA/NHLBI revision, these ORs became slightly stronger. However, neither definition of MetS remained significantly associated with early-onset CAD in multivariate models adjusting for individual components.The presence of MetS imparts a high risk of early-onset clinical CAD, but the prognostic information associated with the syndrome is not greater than the sum of its parts.

Abstract

Prior studies have shown an association between depression and self-rated health among patients with coronary disease. However, the magnitude of the effect of depression on self-rated health compared with that of major clinical events is unknown. Our main objective was to clarify the association between depression and self-rated health using longitudinal data.We performed a prospective cohort study of 2675 postmenopausal women with coronary disease. The primary predictor variable was a 4-state categorical depression variable based on the Burnam depression screen assessed at sequential visits. The outcome variable was self-rated overall health (excellent, very good, or good vs fair or poor).After adjustment for age, comorbidities, prior self-rated health, and interim events, women with depression at both current and prior annual visits had a >5-fold increased odds of fair/poor self-rated health (odds ratio [OR] 5.1, 95% CI 3.8-6.8). New depression was associated with a >2-fold increased odds of fair/poor self-rated health (OR 2.6, 95% CI 2.0-3.4). Having a history of depression at the preceding annual visit but not at the current visit was associated with a slight increased odds of fair/poor self-rated health (OR 1.3, 95% CI 1.0-1.7). The magnitude of the impact of persistent or new depression was comparable to that of recent angina, myocardial infarction, angioplasty, heart failure, or bypass surgery.Women with persistent or new depression are more likely to report fair/poor self-rated health. The magnitude of the impact of persistent or new depression is comparable to that of major cardiac events.

Abstract

A Department of Veterans Affairs Cooperative Study randomized high-risk patients with medically refractory myocardial ischemia, a group largely excluded from previous trials, to urgent revascularization with either percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). The present study examined the cost-effectiveness of PCI versus CABG for these high-risk patients.Of 454 patients at 16 Department of Veterans Affairs medical centers, 445 were available for the economic analysis (218 PCI and 227 CABG patients). Total costs were assessed at 3 and 5 years from the third-party payer's perspective, and effectiveness was measured by survival. After 3 years, average total costs were 63,896 dollars for PCI versus 84,364 dollars for CABG patients, a difference of 20,468 dollars (95% confidence interval [CI] 13,918 dollars to 27,569 dollars). CIs were estimated by bootstrapping. Survival at 3 years was 0.82 for PCI versus 0.79 for CABG patients (P=0.34). Precision of the cost-effectiveness estimates were assessed by bootstrapping. PCI was less costly and more effective at 3 years in 92.6% of the bootstrap replications. After 5 years, average total costs were 81,790 dollars for PCI versus 100,522 dollars for CABG patients, a difference of 18,732 dollars (95% CI 9873 dollars to 27,831 dollars), whereas survival at 5 years was 0.75 for PCI patients versus 0.70 for CABG patients (P=0.21). At 5 years, PCI remained less costly and more effective in 89.4% of the bootstrap replications.PCI was less costly and at least as effective for the urgent revascularization of medically refractory, high-risk patients over 5 years.

Abstract

The Stanford Brief Activity Survey (SBAS), a new two-item physical activity survey, and the Stanford Seven-Day Physical Activity Recall (PAR) questionnaire were administered to men and women, aged 60-69 years, in the Atherosclerotic Disease VAscular functioN and genetiC Epidemiology (ADVANCE) Study. Frequency distributions of SBAS activity levels, as well as a receiver operating curve, were calculated to determine if the SBAS can detect recommended physical activity levels of 150 or more minutes/week at moderate or greater intensity, with PAR minutes/week. Data were collected between December 2001 and January 2004 from 1,010 participants (38% women) and recorded. Subjects were 65.8 (standard deviation: 2.8) years of age, 77% were married, 55% were retired, 23% were college graduates, and 68% were Caucasian. SBAS scores related significantly in an expected manner to PAR minutes/week (p < 0.01), energy expenditure (kcal/kg per day) (p < 0.01), and selected cardiovascular disease risk biomarkers (p < 0.01). The SBAS of physical activity at moderate intensity had a sensitivity of 0.73 and a specificity of 0.61. The SBAS is a quick assessment of the usual amount and intensity of physical activity that a person performs throughout the day. The SBAS needs further validation in other populations but demonstrated the potential of being a reasonably valid and inexpensive tool for quickly assessing habitual physical activity in large-scale epidemiology studies and clinical practice.

Abstract

Diabetes mellitus and coronary artery disease (CAD) commonly coexist, and thus effective, cost-effective management strategies are needed. Intensive management of diabetes has been shown to increase medical costs while yielding better outcomes, with an acceptable cost-effectiveness ratio of <50,000 dollars per life-year added. On the basis of clinical trial findings in the 1970s and 1980s, coronary bypass surgery was cost-effective compared with medical therapy in the treatment of extensive CAD. Few trials have compared angioplasty with medical therapy, and its cost-effectiveness is not well established. The economic outcomes of contemporary coronary revascularization, especially angioplasty, compared with contemporary medical therapy must be evaluated. The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial will collect extensive economic data and examine the cost-effectiveness of alternative strategies to manage diabetes and CAD in patients with both disorders.

Abstract

Economic outcomes are now included in many contemporary randomized trials and provide an additional dimension to the assessment of interventions. Economic data collection and analysis pose several methodologic challenges, however.This paper reviews methods of incorporating economic outcomes in clinical trials.Data on medical resource utilization and cost can readily be collected along with data on clinical outcomes. The cost of planned interventions can be measured with reasonable accuracy, but costs due to unplanned clinical events are more difficult to measure reliably. The total cost depends critically on these relatively infrequent, yet costly, adverse outcomes, which may partially, or even completely, offset any difference between the planned costs of the randomized therapies. Newer therapies are typically more expensive than older therapies, so the most important question is whether patient outcomes are improved sufficiently to justify the added expense. Cost-effectiveness analysis helps gauge the value provided by a new therapy. The cost-effectiveness of an intervention compared with an alternative is defined as the ratio of the incremental costs and the incremental clinical benefits, measured as dollars per quality-adjusted life-year added. The follow-up period in most clinical trials is generally long enough to measure the added cost of therapy, but may not capture the full benefits of treatment. The limited time horizon of clinical trials makes it necessary to use a model to extrapolate the observed effect of treatment and project the increase in life expectancy. The resulting cost-effectiveness ratio is sensitive to assumptions about the long-term efficacy of treatment, particularly whether the treatment effect will continue or dissipate over time.Economic outcomes can be measured alongside clinical outcomes in randomized trial. While the use of cost-effectiveness models falls outside the strictly empirical, within-trial analysis framework that is embraced by most clinical trialists, it provides an explicit approach to assessing whether the intervention under study provides a clinically meaningful improvement in outcome that is worthwhile.

Abstract

Demand for economic evaluations in multinational clinical trials is increasing, but there is little consensus about how such studies should be conducted and reported. At a workshop in Durham, North Carolina, we sought to identify areas of agreement about how the primary findings of economic evaluations in multinational clinical trials should be generated and presented. In this paper, we propose a framework for classifying multinational economic evaluations according to (a) the sources of an analyst's estimates of resource use and clinical effectiveness and (b) the analyst's method of estimating costs. We review existing studies in the cardiology literature in the context of the proposed framework. We then describe important methodological and practical considerations in conducting multinational economic evaluations and summarize the advantages and disadvantages of each approach. Finally, we describe opportunities for future research. Delineation of the various approaches to multinational economic evaluation may assist researchers, peer reviewers, journal editors, and decision makers in evaluating the strengths and limitations of particular studies.

Abstract

The implantable cardioverter defibrillator (ICD) is a costly new treatment for patients at high risk of sudden cardiac death. Randomized trials of the ICD showed it to be effective in some groups of patients but not in others. While new trials testing the ICD were ongoing to clarify the evidence, policymakers faced immediate decisions about providing insurance coverage for the device. The high cost of ICDs, the large population of patients potentially eligible to receive them, the potential to reduce preventable deaths, and the unsettled state of the medical evidence provided a challenge to evidence-based medicine and to policymakers.

Abstract

Patients with pulmonary arterial hypertension (PAH) often present with dyspnea and severe functional limitations, but their health-related quality of life (HRQOL) has not been studied extensively. This study describes HRQOL in a cohort of patients with PAH.Cross-sectional study.A tertiary care, university hospital-based, pulmonary hypertension (PH) clinic.We studied HRQOL in 53 patients with PAH (mean age, 47 years; median duration of disease, 559 days). Eighty-three percent were women, 53% received epoprostenol, and 72% reported moderate-to-severe functional limitations with a New York Heart Association class 3 or 4 at enrollment.We examined HRQOL by administering the Nottingham Health Profile, Congestive Heart Failure Questionnaire, and Hospital Anxiety and Depression Scale. We used the Visual Analog Scale and standard gamble (SG) techniques to measure preferences for current health (utilities). Compared with population norms, participants reported moderate-to-severe impairment in multiple domains of HRQOL, including physical mobility, emotional reaction, pain, energy, sleep, and social isolation. Mean SG utilities were 0.71, suggesting that, on average, participants were willing to accept a 29% risk of death in order to be cured of PH.PAH is a devastating condition that affects predominately young women in the prime of their life. Understanding HRQOL and preferences are important in the care and management of these patients. Compared with population norms, patients with PAH have substantial functional and emotional limitations that adversely affect their HRQOL.

Abstract

Cardiovascular screening of athletes is a challenging aspect of the preparticipation evaluation. While sudden cardiac death in young athletes is uncommon, preparticipation screening may identify some predisposing conditions that place individuals at increased risk. The most common pre-existing cardiac abnormalities in athletes causing sudden death in the United States are hypertrophic cardiomyopathy, congenital coronary anomalies, and Marfan syndrome. Preparticipation cardiovascular screening should pursue any history of cardiac symptoms or family history of premature cardiac disease, as well as abnormal cardiovascular physical findings. Positive findings should be investigated; an electrocardiogram, echocardiogram, or consultation with a specialist should be considered. Recommendations are then available to guide athletic participation according to the cardiovascular diagnosis.

Abstract

To compare the cost-effectiveness of surgical and angioplasty-based coronary artery revascularization techniques, in particular, angioplasty with primary stenting.We used data from the Study of Economics and Quality of Life, a substudy of the Bypass Angioplasty Revascularization Investigation (BARI), to measure the outcomes and costs of angioplasty and bypass surgery in patients with multivessel coronary artery disease who had not undergone prior coronary artery revascularization. Using a Markov decision model, we updated the outcomes and costs to reflect technology changes since the time of enrollment in BARI, and projected the lifetime costs and quality-adjusted life-years (QALYs) for the two procedures from the time of initial treatment through death. We accounted for the effects of improved procedural safety and efficiency, and prolonged therapeutic effects of both surgery and stenting. This study was conducted from a societal perspective.Surgical revascularization was less costly and resulted in better outcomes than catheter-based intervention including stenting. It remained the preferred strategy after adjusting the stent outcomes to eliminate the costs and events associated with target lesion restenosis. Among angioplasty-based strategies, primary stent use cost an additional 189,000 US dollars per QALY gained compared with a strategy that reserved stent use for treatment of suboptimal balloon angioplasty results.Bypass surgery results in better outcomes than angioplasty in patients with multivessel disease, and at a lower cost.

Abstract

The risk of cardiovascular mortality is higher among black women than white women, and the reasons for this disparity are largely unexplored. We sought to evaluate differences in medical care and clinical outcomes among black and white women with established coronary artery disease.Among the 2699 women enrolled in the Heart and Estrogen/progestin Replacement Study (HERS), we used Cox proportional hazards models to determine the association of race with risk of coronary heart disease (CHD) events independent of major cardiovascular risk factors or medical therapies. During an average of 4.1 years of follow-up, CHD events were twice as likely in black compared with white women (6.4 versus 3.1 per 100 person-years, hazard ratio, 2.1; 95% confidence interval, 1.5 to 2.8; P<0.001). Black women had higher rates of hypertension, diabetes, and hypercholesterolemia, yet were less likely to receive aspirin or statins. Black women less often had optimal blood pressure (56% versus 63%; P=0.01) and LDL cholesterol (30% versus 38%; P=0.04) control at baseline and during follow-up. After adjusting for these and other differences, black women still had >50% higher CHD event risk (hazard ratio, 1.52; 95% confidence interval, 1.1 to 2.1; P=0.03).In a large cohort of women with heart disease, black women less often received appropriate preventive therapy and adequate risk factor control despite a greater CHD event risk. Interventions to improve appropriate therapy and risk factor control in all women, and especially black women, are needed.

Abstract

Little is known regarding the extent to which patient-reported health status, including symptom burden, physical limitation, and quality of life, is determined by psychosocial vs physiological factors among patients with chronic disease.To compare the contributions of depressive symptoms and measures of cardiac function to the health status of patients with coronary artery disease.Cross-sectional study of 1024 adults with stable coronary artery disease recruited from outpatient clinics in the San Francisco Bay Area between September 2000 and December 2002. Main Measures Measurement of depressive symptoms using the Patient Health Questionnaire (PHQ); assessment of cardiac function by measuring left ventricular ejection fraction on echocardiography, exercise capacity on treadmill testing, and ischemia on stress echocardiography; and measurement of a range of health status outcomes, including symptom burden, physical limitation, and quality of life, using the Seattle Angina Questionnaire. Participants were also asked to rate their overall health as excellent, very good, good, fair, or poor.Of the 1024 participants, 201 (20%) had depressive symptoms (PHQ score > or =10). Participants with depressive symptoms were more likely than those without depressive symptoms to report at least mild symptom burden (60% vs 33%; P

Abstract

Contemporary clinical trials commonly measure quality of life and medical costs to establish whether therapies are both effective and cost effective. Cost-effectiveness analysis, however, requires a measure of patient utility or preferences for various health states. Because utilities are not often measured directly, we sought to develop a method of translating standard quality-of-life scales into a patient utility measure.Five hundred fifty-three patients enrolled in the Bypass Angioplasty Revascularization Investigation Study of Economics and Quality of Life completed a battery of quality-of-life measures and a time trade-off utility assessment an average of 7.3 years after random assignment.The mean time trade-off score was 8.54 (SD = 2.53) out of a maximum of 10; median score was 9.95. The distribution of scores was skewed, with 12% of patients at the highest possible score of 10. Patients with recurrent angina had significantly lower time trade-off scores than patients without angina (mean 7.03 vs 8.70, P

Abstract

Economic endpoints have been increasingly included in long-term clinical trials, but they pose several methodologic challenges, including how best to collect, describe, analyse and interpret medical cost data. Cost of care can be measured by converting billed charges, performing detailed micro-costing studies, or by measuring use of key resources and assigning cost weights to each resource. The latter method is most commonly used, with cost weights based either on empirical regression models or administratively determined reimbursement rates. In long-term studies, monetary units should be adjusted to reflect cost inflation and discounting. The temporal pattern of accumulating costs can be described using a modification of the Kaplan-Meier curve. Regression analyses to evaluate factors associated with cost are best performed on the log of costs due to their typically skewed distribution.Cost-effectiveness analysis attempts to measure the value of a new therapy by calculating the difference in cost between the new therapy and the standard therapy, divided by the difference in benefit between the new therapy and the standard therapy. The cost-effectiveness ratio based on the results of a randomized trial may change substantially with longer follow-up intervals, particularly for therapies that are initially expensive but eventually improve survival. A model that projects long-term patterns of cost and survival expected beyond the end of completed follow-up can provide an important perspective in the setting of limited trial duration.

Abstract

Patients at high risk of sudden cardiac death, yet at low risk of nonsudden death, might be ideal candidates for antiarrhythmic drugs or devices. Most previous studies of prognostic markers for sudden cardiac death have ignored the competitive risk of nonsudden cardiac death. The goal of the present study was to evaluate the ability of clinical factors to distinguish the risks of sudden and nonsudden cardiac death.We identified all deaths during a 3.3-year follow-up of 30,680 patients discharged alive after admission to the cardiac care unit of a Seattle hospital. Detailed chart reviews were conducted on 1093 subsequent out-of-hospital sudden deaths, 973 nonsudden cardiac deaths, and 442 randomly selected control patients.Patients who died in follow-up (suddenly or nonsuddenly) were significantly different for many clinical factors from control patients. In contrast, patients with sudden cardiac death were insignificantly different for most clinical characteristics from patients with nonsudden cardiac death. The mode of death was 20% to 30% less likely to be sudden in women, patients who had angioplasty or bypass surgery, and patients prescribed beta-blockers. The mode of death was 20% to 30% more likely to be sudden in patients with heart failure, frequent ventricular ectopy, or a discharge diagnosis of acute myocardial infarction. A multivariable model had only modest predictive capacity for mode of death (c-index of 0.62).Standard clinical evaluation is much better at predicting overall risk of death than at predicting the mode of death as sudden or nonsudden.

Abstract

There are few data from community-based evaluations of outcomes after a life-threatening ventricular arrhythmia (LTVA). We evaluated patients' quality of life (QOL) and medical costs after hospitalization and treatment for their first episode of an LTVA.We prospectively evaluated QOL by use of the Duke Activity Status Index (DASI), Medical Outcomes Study SF-36 mental health and vitality scales, the Cardiac Arrhythmia Suppression Trial (CAST) symptom scale, and resource use in patients discharged after a first episode of an LTVA in a managed care population of 2.4 million members.We enrolled 264 subjects with new cases of LTVA. Although functional status initially decreased compared with self-reports of pre-event functional status, both functional status and symptom levels improved significantly during the study period. These improvements were greater in patients receiving an implantable cardioverter defibrillator (ICD) than in patients receiving amiodarone. Ratings of mental health and vitality were not significantly different between the treatment groups and did not change significantly during follow-up. The total 2-year medical costs were higher for patients receiving an ICD than for patients receiving amiodarone, despite lower costs during the follow-up period for the patients receiving an ICD.New onset of an LTVA has a substantial negative initial impact on QOL. With therapy, most patients have improvements in their QOL and symptom level, possibly more so after treatment with an ICD. The costs of treating these patients are very high.

Abstract

The use of coronary angiography and revascularization is lower than expected among black patients. It is uncertain whether use of other cardiac procedures also varies according to race and ethnicity and whether outcomes are affected.We analyzed discharge abstracts from all nonfederal hospitals in California of patients hospitalized for a primary diagnosis of ventricular tachycardia or ventricular fibrillation between 1992 and 1994. We compared mortality rates and use of electrophysiologic study (EPS) and implantable cardioverter-defibrillator (ICD) procedures according to the race and ethnicity of the patient.Among 8713 patients admitted with ventricular tachycardia or ventricular fibrillation, 29% (n = 2508) had a subsequent EPS procedure, and 9% (n = 818) had an ICD implanted. After controlling for potential confounding factors, we found that black patients were significantly less likely than white patients to undergo EPS (odds ratio 0.72, CI 0.56-0.92) or ICD implantation (odds ratio 0.39, CI 0.25-0.60). Blacks discharged alive from the initial hospital admission had higher mortality rates over the next year than white patients, even after controlling for multiple confounding risk factors (risk ratio 1.18, CI 1.03-1.36). The use of EPS and ICD procedures was also significantly affected by several other factors, most notably by on-site procedure availability but also by age, sex, and insurance status.In a large population of patients hospitalized for ventricular arrhythmia, blacks had significantly lower rates of utilization for EPS and ICD procedures and higher subsequent mortality rates.

Abstract

The patterns of adoption of the implantable cardioverter defibrillator (ICD) and the outcomes of its use have not been well documented in general, unselected populations. The purpose of this study was to document the impact of the ICD in widespread clinical practice.We identified ICD recipients by use of the hospital discharge databases of Medicare beneficiaries for 1987 through 1995 and of California residents for 1991 through 1995. The index admission for each patient was linked to previous and subsequent admissions and to mortality files to create a longitudinal patient profile.The rate of ICD implantations increased >10-fold between 1987 and 1995, as both the number of hospitals performing the procedure and the volume of ICD implantations per hospital rose. Mortality rates within 30 days of ICD implantation decreased from 6.0% to 1.9%, and mortality rates within 1 year fell from 19.3% to 11.4%. Surgical interventions to revise or replace the ICD within the first year remained about 5%, however, and cumulative expenditures at 1 year ($46,000-$51,000) changed very little. ICD implantation rates varied >3-fold among different regions of the United States.ICD use has expanded markedly during the study period, with improved mortality rates, but medical expenditures and rates of surgical revision remain high for ICD recipients.

Abstract

Sudden cardiac death is a prominent feature of the natural history of heart disease. The efficacy of antiarrhythmic drugs and devices in preventing sudden death and reducing total mortality is uncertain.We reviewed randomized trials and quantitative overviews of type I and type III antiarrhythmic drugs. We also reviewed the randomized trials of implantable cardioverter defibrillators and combined these outcomes in a quantitative overview.Randomized trials of type I antiarrhythmic agents used as secondary prevention after myocardial infarction show an overall 21% increase in mortality rate. Randomized trials of amiodarone suggest a 13% to 19% decrease in mortality rate, and sotalol has been effective in several small trials. Trials of pure type III agents, however, have shown no mortality benefit. An overview of implantable defibrillator trials shows a 24% reduction in mortality rate (CI 15%-33%) compared with alternative therapy, most often amiodarone.Amiodarone is effective in reducing the total mortality rate by 13% to 19%, and the implantable defibrillator reduces the mortality rate by a further 24%.

Abstract

Implantable cardioverter defibrillators (ICDs) effectively prevent sudden cardiac death, but selection of appropriate patients for implantation is complex. We evaluated whether risk stratification based on risk of sudden cardiac death alone was sufficient to predict the effectiveness and cost-effectiveness of the ICD.We developed a Markov model to evaluate the cost-effectiveness of ICD implantation compared with empiric amiodarone treatment. The model incorporated mortality rates from sudden and nonsudden cardiac death, noncardiac death and costs for each treatment strategy. We based our model inputs on data from randomized clinical trials, registries, and meta-analyses. We assumed that the ICD reduced total mortality rates by 25%, relative to use of amiodarone.The relationship between cost-effectiveness of the ICD and the total annual cardiac mortality rate is U-shaped; cost-effectiveness becomes unfavorable at both low and high total cardiac mortality rates. If the annual total cardiac mortality rate is 12%, the cost-effectiveness of the ICD varies from $36,000 per quality-adjusted life-year (QALY) gained when the ratio of sudden cardiac death to nonsudden cardiac death is 4 to $116,000 per QALY gained when the ratio is 0.25.The cost-effectiveness of ICD use relative to amiodarone depends on total cardiac mortality rates as well as the ratio of sudden to nonsudden cardiac death. Studies of candidate diagnostic tests for risk stratification should distinguish patients who die suddenly from those who die nonsuddenly, not just patients who die suddenly from those who live.

Abstract

Treatment options for patients with ventricular arrhythmias have undergone major changes in the last 2 decades. Trends in use of invasive procedures, clinical outcomes, and expenditures have not been well documented.We used administrative databases of Medicare beneficiaries from 1985 to 1995 to identify patients hospitalized with ventricular arrhythmias. We created a longitudinal patient profile by linking the index admission with all earlier and subsequent admissions and with death records.Approximately 85,000 patients aged > or =65 years went to hospitals in the United States with ventricular arrhythmias each year, and about 20,000 lived to admission. From 1987 to 1995, the use of electrophysiology studies and implantable cardioverter defibrillators in patients who were hospitalized grew substantially, from 3% to 22% and from 1% to 13%, respectively. Hospital expenditures rose 8% per year, primarily because of the increased use of invasive procedures. Survival improved, particularly in the medium term, with 1-year survival rates increasing between 1987 and 1994 from 52.9% to 58.3%, or half a percentage point each year.Survival of patients who sustain a ventricular arrhythmia is poor, but improving. For patients who are admitted, more intensive treatment has been accompanied by increased hospital expenditures.

Abstract

The implantable cardioverter defibrillator has been assessed in randomized trials, but the generalizability of trial results to broader clinical settings is unclear. Our purpose was to evaluate the outcomes and costs of defibrillator use in an unselected population.We identified 125,892 Medicare patients who were discharged between 1987 and 1995 after hospitalization with a primary diagnosis of ventricular tachycardia or ventricular fibrillation, 7789 of whom (6.2%) received a defibrillator. We used a multivariable propensity score that included patient and hospital characteristics to match pairs of patients, in which one patient received a defibrillator and the other did not. We compared mortality and costs in these 7612 matched pairs during 8 years of follow-up.Patients who received a defibrillator were more likely to be younger, white, male, and urban dwelling, and to have ischemic heart disease, heart failure, or a history of ventricular fibrillation. In the matched-pairs analysis, those who received a defibrillator had significantly lower mortality: 11% versus 19% at 1 year (odds ratio [OR] = 0.57; 95% confidence interval [CI]: 0.51 to 0.63), 20% versus 30% at 2 years (OR = 0.66; 95% CI: 0.60 to 0.72), and 28% versus 39% at 3 years (OR = 0.70; 95% CI: 0.63 to 0.77). These patients also had lower mortality at 8 years (P = 0.0001), although this advantage over patients who received medical treatment only decreased over time. Expenditures among defibrillator recipients were consistently higher, with a cost-effectiveness ratio of $78,400 per life-year gained.The use of implantable defibrillators was associated with significantly lower mortality and higher costs, whereas the cost-effectiveness was higher than many, but not all, generally accepted therapies.

Abstract

Economic endpoints are increasingly common in randomized clinical trials. As a relatively new addition to the field, methods of measuring and analyzing cost data are still evolving. These developments will be stimulated by the demands of the public for efficient and effective medical care, which will be based on the findings of clinical trials.

Abstract

Reimbursement for the routine care of patients enrolled in clinical trials is controversial. Our objective was to determine the added medical costs, if any, associated with enrollment in a randomized clinical trial.We analyzed data from the Myocardial Infarction Triage and Intervention (MITI) Trial (1988-1991) and the registry of all patients admitted to 19 Seattle area coronary care units (1988-1993). The major trial entry criteria were age 35 to 71 years, symptom duration 15 minutes to 6 hours, and acute myocardial infarction on electrocardiogram. The trial group consisted of 264 of 324 randomized patients who received thrombolytics and had available cost data. From 11,932 registry patients, we identified a control group who met trial entry criteria but who were not enrolled because of logistic barriers or presentation outside the trial enrollment period, 335 of whom received thrombolytics and had available cost data. The groups were compared for total cost for initial hospitalization, with and without multivariable adjustment for baseline characteristics.Total hospital cost was not different between trial patients (median $11,516) and control subjects (median $14,200) (trial/control mean cost ratio 0.91 [95% CI 0.82-1.02]). Participation in the trial had an insignificant effect on costs in the multivariable model (cost ratio 1.04, 95% CI 0.95-1.16). Significant predictors of cost included hospital of admission, length of stay, and coronary revascularization procedures.Participation in the MITI randomized trial had no effect on the cost of routine care.

Abstract

Clinical trials have shown that implantable cardioverter defibrillators (ICDs) improve survival in patients with sustained ventricular arrhythmias.To determine the efficacy necessary to make prophylactic ICD or amiodarone therapy cost-effective in patients with myocardial infarction.Markov model-based cost utility analysis.Survival, cardiac death, and inpatient costs were estimated on the basis of the Myocardial Infarction Triage and Intervention registry. Other data were derived from the literature.Patients with past myocardial infarction who did not have sustained ventricular arrhythmia.Lifetime.Societal.ICD or amiodarone compared with no treatment.Life-years, quality-adjusted life-years (QALYs), costs, number needed to treat, and incremental cost-effectiveness.Compared with no treatment, ICD use led to the greatest QALYs and the highest expenditures. Amiodarone use resulted in intermediate QALYs and costs. To obtain acceptable cost-effectiveness thresholds (=$75,000/QALY), ICDs had to reduce arrhythmic death by 50% and amiodarone had to reduce total death by 7% in patients with depressed ejection fraction.For moderate efficacies, in patients with ejection fractions less than or equal to 0.3, 0.31 to 0.4, and greater than 0.4, the cost-effectiveness of amiodarone compared with no therapy was $43,100/QALY, $66,500/QALY, and $132,500/QALY, respectively, and the cost-effectiveness of ICD compared with amiodarone was $71,800/QALY, $195,700/QALY, and $557,900/QALY, respectively.Use of ICD or amiodarone in patients with past myocardial infarction and severely depressed left ventricular function may provide substantial clinical benefit at an acceptable cost. These results highlight the importance of clinical trials of ICDs in patients with low ejection fractions who have had myocardial infarction.

Abstract

This study was designed to compare the prognostic value of an abnormal troponin level derived from studies of patients with non-ST elevation acute coronary syndromes (ACS).Risk stratification for patients with suspected ACS is important for determining need for hospitalization and intensity of treatment.We identified clinical trials and cohort studies of consecutive patients with suspected ACS without ST-elevation from 1966 through 1999. We excluded studies limited to patients with acute myocardial infarction and studies not reporting mortality or troponin results.Seven clinical trials and 19 cohort studies reported data for 5,360 patients with a troponin T test and 6,603 with a troponin I test. Patients with positive troponin (I or T) had significantly higher mortality than those with a negative test (5.2% vs. 1.6%, odds ratio [OR] 3.1). Cohort studies demonstrated a greater difference in mortality between patients with a positive versus negative troponin I (8.4% vs. 0.7%, OR 8.5) than clinical trials (4.8% if positive, 2.1% if negative, OR 2.6, p = 0.01). Prognostic value of a positive troponin T was also slightly greater for cohort studies (11.6% mortality if positive, 1.7% if negative, OR 5.1) than for clinical trials (3.8% if positive, 1.3% if negative, OR 3.0, p = 0.2)In patients with non-ST elevation ACS, the short-term odds of death are increased three- to eightfold for patients with an abnormal troponin test. Data from clinical trials suggest a lower prognostic value for troponin than do data from cohort studies.

Abstract

Several cohort studies in populations without coronary heart disease have demonstrated that up to 40% of incident myocardial infarctions are clinically unrecognized.To determine the incidence of unrecognized myocardial infarction in women with coronary heart disease in the Heart and Estrogen/progestin Replacement Study (HERS).Randomized, double-blind, placebo-controlled trial of conjugated estrogens plus medroxyprogesterone or identical placebo with 4.1 years of follow-up.Outpatient and community settings at 20 U.S. clinical centers.2763 postmenopausal women younger than 80 years of age with coronary heart disease and an intact uterus.Annual electrocardiograms were obtained for all participants during follow-up (mean, 4.1 years) and were evaluated by using the NOVACODE computer algorithm and visual confirmation. A total of 13 715 electrocardiograms were obtained. Suspected unrecognized myocardial infarctions were investigated by comparing a participant's previous surveillance electrocardiograms with the electrocardiograms obtained from all of her intervening hospitalizations. Characteristics of patients with recognized and unrecognized myocardial infarction were compared.Among the 256 nonfatal myocardial infarctions, 11 were unrecognized (4.3% [95% CI, 2.2% to 7.6%]). Seven occurred in women assigned to placebo and 4 occurred in women assigned to hormone therapy (P > 0.2). Women with unrecognized myocardial infarction were less likely to have diabetes mellitus or previous angina and were more likely to have had previous bypass surgery compared with women who had clinically recognized myocardial infarction.The incidence of unrecognized myocardial infarction in women with coronary disease was far lower than that observed in previous studies of populations without coronary heart disease.

Abstract

Previous studies have shown that coronary artery bypass surgery reduces the risk of cardiac complications after noncardiac surgery. Whether coronary angioplasty provides equivalent protection is not known.Patients were randomly assigned to undergo cardiac artery bypass surgery or angioplasty as part of the Bypass Angioplasty Revascularization Investigation trial. All subsequent noncardiac surgeries during a mean (+/- SD) follow-up of 7.7 years were recorded among participants in the ancillary Study of Economics and Quality of Life. Rates of mortality and nonfatal myocardial infarction, length of stay, and hospital costs were compared by the original randomized assignment.A total of 501 patients had noncardiac surgery at a median of 29 months after their most recent coronary revascularization procedure. Mortality and nonfatal myocardial infarction within 30 days of the first noncardiac surgery occurred in 4 of the 250 of the surgery-assigned patients and in 4 of the 251 of the angioplasty-assigned patients (P = 1.0). There were no significant differences in the mean length of hospital stay (6.3 +/- 6.7 versus 6.2 +/- 6.8 days; P = 0.47) or hospital cost ($8,920 +/- $11,511 versus $7,785 +/- $7,643; P = 0.33) between the surgery and angioplasty groups. Similar results were obtained when subsequent noncardiac procedures were included in the analysis.Rates of myocardial infarction and death after noncardiac surgery are similarly low after contemporary bypass surgery or angioplasty in patients with multivessel coronary artery disease.

Abstract

Radiofrequency ablation is an established but expensive treatment option for many forms of supraventricular tachycardia. Most cases of supraventricular tachycardia are not life-threatening; the goal of therapy is therefore to improve the patient's quality of life.To compare the cost-effectiveness of radiofrequency ablation with that of medical management of supraventricular tachycardia.Markov model.Costs were estimated from a major academic hospital and the literature, and treatment efficacy was estimated from reports from clinical studies at major medical centers. Probabilities of clinical outcomes were estimated from the literature. To account for the effect of radiofrequency ablation on quality of life, assessments by patients who had undergone the procedure were used.Cohort of symptomatic patients who experienced 4.6 unscheduled visits per year to an emergency department or a physician's office while receiving long-term drug therapy for supraventricular tachycardia.Patient lifetime.Societal.Initial radiofrequency ablation, long-term antiarrhythmic drug therapy, and treatment of acute episodes of arrhythmia with antiarrhythmic drugs.Costs, quality-adjusted life-years, life-years, and marginal cost-effectiveness ratios.Among patients who have monthly episodes of supraventricular tachycardia, radiofrequency ablation was the most effective and least expensive therapy and therefore dominated the drug therapy options. Radiofrequency ablation improved quality-adjusted life expectancy by 3.10 quality-adjusted life-years and reduced lifetime medical expenditures by $27 900 compared with long-term drug therapy. Long-term drug therapy was more effective and had lower costs than episodic drug therapy.The findings were highly robust over substantial variations in assumptions about the efficacy and complication rate of radiofrequency ablation, including analyses in which the complication rate was tripled and efficacy was decreased substantially.Radiofrequency ablation substantially improves quality of life and reduces costs when it is used to treat highly symptomatic patients. Although the benefit of radiofrequency ablation has not been studied in less symptomatic patients, a small improvement in quality of life is sufficient to give preference to radiofrequency ablation over drug therapy.

Abstract

Stents are now used in the majority of percutaneous coronary revascularization procedures. It is not clear whether the higher initial cost of stenting is later repaid by reducing costly complications and repeat revascularization procedures, especially for patients with multivessel disease.To project the long-term costs of using coronary stents, angioplasty, or bypass surgery to treat patients with multivessel coronary artery disease, we developed a decision model based on the outcomes documented in the Bypass Angioplasty Revascularization Investigation (BARI) randomized trial of coronary artery bypass grafting (CABG) and percutaneous transluminal coronary angioplasty (PTCA). We studied 2 clinical strategies: provisional stenting of suboptimal PTCA results and primary stenting of all angiographically eligible lesions. The cost of CABG was also updated to reflect contemporary practice.Provisional stenting had lower projected costs over a 4-year period than either traditional PTCA (-$1742, or -3.4%) or contemporary CABG (-$832, or -1.7%), mostly because of reductions in emergency CABG after PTCA. In contrast, primary stenting had higher projected costs over a 4-year period than either PTCA (+$333, or +0. 7%) or contemporary CABG (+$1243, or +2.5%), mainly because of the higher initial procedure costs. These results were not substantially altered when we systematically varied the key parameters of the models in 1-way and 2-way sensitivity analyses.A primary stenting strategy in patients with multivessel disease has higher projected long-term costs than CABG. In contrast, a provisional stenting strategy in multivessel disease has lower projected costs than either PTCA or CABG.

Abstract

To compare seven-year survival in the Bypass Angioplasty Revascularization Investigation (BARI) patients randomly assigned to percutaneous transluminal coronary angioplasty (PTCA) versus coronary artery bypass grafting (CABG).The primary results of BARI reported no significant difference in five-year survival between CABG and PTCA groups. However, among patients with treated diabetes mellitus, a subgroup not specified a priori, a striking difference was seen in favor of CABG.Symptomatic patients with multivessel disease (n = 1,829) were randomly assigned to initial treatment strategy of CABG or PTCA and followed for an average of 7.8 years. The intention-to-treat principle was used to extend the initial five-year BARI treatment comparisons.Kaplan-Meier estimates of seven-year survival for the total population were 84.4% for CABG and 80.9% for PTCA (p = 0.043). This difference could be explained by the 353 patients with treated diabetes mellitus for whom estimates of seven year survival were 76.4% CABG and 55.7% PTCA (p = 0.0011). Among the remaining 1,476 patients without treated diabetes, survival was virtually identical by assigned treatment (86.4% CABG, 86.8% PTCA, p = 0.72). The PTCA group had substantially higher subsequent revascularization rates than the CABG group (59.7% vs. 13.1%, p < 0.001); however, the changes between the five- and seven-year rates were similar for the two groups.At seven years, there was a statistically significant survival advantage for patients randomized to CABG compared with PTCA. Among patients with treated diabetes mellitus, the benefit of CABG over PTCA seen at five years was more pronounced at seven years; among nondiabetic patients, there was essentially no treatment difference.

Abstract

Cardiac procedures are performed less frequently in Canada than in the United States (US), yet rates of cardiac death and myocardial infarction are similar. We therefore sought to compare long-term symptoms and quality of life in Canadian and American patients undergoing initial coronary revascularization. The 161 patients enrolled in the Bypass Angioplasty Revascularization Investigation at the Montreal Heart Institute were compared with 934 patients enrolled at 7 US sites. Patients' outcomes were documented for 5 years after random assignment to percutaneous transluminal coronary angioplasty or coronary artery bypass graft surgery. Functional status was assessed using the Duke Activity Status Index. Canadian patients were significantly younger and had more angina at study entry. Death and nonfatal myocardial infarction were not significantly different between Canadian and US patients after adjustment for baseline risk. Canadian patients had significantly greater improvements in functional status at 1-year follow-up (Duke Activity Status Index score + 13.5 vs. + 6.0, p = 0.002), but this difference progressively narrowed over 5 years. Angina was equally prevalent in Canadian and US patients at 1 year (16% vs. 19%), but significantly more prevalent in Canadian patients at 5 years (36% vs. 16%, p = 0.001). Repeat revascularization procedures were performed less often over 5 years among Canadian patients (26% vs. 34%, p = 0.08), especially coronary artery bypass graft surgery after initial percutaneous transluminal coronary angioplasty (18% vs. 32%, p = 0.03). These results suggest more anginal symptoms are required in Canada before coronary revascularization, but as a result Canadians receive greater improvements in quality of life after the procedure.

Abstract

In a retrospective survey of 161 highly symptomatic patients, we found significant improvements in symptoms, patient utility, and use of medical care services after radiofrequency ablation for atrioventricular nodal reentrant tachycardia.

Abstract

Which drug is most effective as a first-line treatment for stable angina is not known.To compare the relative efficacy and tolerability of treatment with beta-blockers, calcium antagonists, and long-acting nitrates for patients who have stable angina.We identified English-language studies published between 1966 and 1997 by searching the MEDLINE and EMBASE databases and reviewing the bibliographies of identified articles to locate additional relevant studies.Randomized or crossover studies comparing antianginal drugs from 2 or 3 different classes (beta-blockers, calcium antagonists, and long-acting nitrates) lasting at least 1 week were reviewed. Studies were selected if they reported at least 1 of the following outcomes: cardiac death, myocardial infarction, study withdrawal due to adverse events, angina frequency, nitroglycerin use, or exercise duration. Ninety (63%) of 143 identified studies met the inclusion criteria.Two independent reviewers extracted data from selected articles, settling any differences by consensus. Outcome data were extracted a third time by 1 of the investigators. We combined results using odds ratios (ORs) for discrete data and mean differences for continuous data. Studies of calcium antagonists were grouped by duration and type of drug (nifedipine vs nonnifedipine).Rates of cardiac death and myocardial infarction were not significantly different for treatment with beta-blockers vs calcium antagonists (OR, 0.97; 95% confidence interval [CI], 0.67-1.38; P = .79). There were 0.31 (95% CI, 0.00-0.62; P = .05) fewer episodes of angina per week with beta-blockers than with calcium antagonists. beta-Blockers were discontinued because of adverse events less often than were calcium antagonists (OR, 0.72; 95% CI, 0.60-0.86; P

Abstract

Patients who undergo coronary angioplasty have a shorter convalescence than those who undergo coronary bypass surgery. This may improve subsequent employment.To compare employment patterns after coronary angioplasty or surgery.Multicenter, randomized clinical trial.Seven tertiary care hospitals.409 employed patients with multivessel coronary artery disease.Coronary bypass surgery or balloon angioplasty.Time to return to work and time spent working during 4 years of follow-up.Patients who underwent angioplasty returned to work 6 weeks sooner than patients who underwent coronary bypass surgery (P < 0.001), but long-term employment did not differ significantly (P > 0.2). Long-term employment was significantly lower among patients who were 60 to 64 years of age (P < 0.001), those who worked less than full-time at study entry (P < 0.001), and those who had less formal education (P = 0.005). Patients with only one source of health insurance were more likely to continue working (P = 0.005).Faster recovery after angioplasty speeds return to work but does not improve long-term employment, which is primarily associated with nonmedical factors.

Abstract

Coronary bypass surgery often leads to short-term cognitive dysfunction, whereas coronary angioplasty does not. Perioperative cognitive dysfunction usually resolves, although a subgroup of surgical patients may continue to exhibit long-term cognitive dysfunction. The purpose of this study was to compare cognitive function 5 years after randomization to a strategy of either initial coronary surgery or initial angioplasty.Five centers in the Bypass Angioplasty Revascularization Investigation participated in this ancillary study. Patients with multivessel coronary disease randomized to angioplasty or surgery were eligible at the time of their 5-year clinic visit. A battery of five measures previously shown to be sensitive to perioperative changes in cognitive function was administered, including the Logical and Figural Memory Scales from the Wechsler Memory Scale, the Digit Symbol and Digit Span subtests from the Wechsler Adult Intelligence Scale, and Part B of the Reitan Trail Making Test. The 125 study patients were generally similar to the 133 patients who were eligible but did not participate, although study participants were significantly younger (P=.003). The 64 patients randomly assigned to angioplasty had baseline characteristics similar to those of 61 patients randomly assigned to surgery. Cognitive function scores were not significantly different between angioplasty or surgery patients in an intention-to-treat analysis (P=.57). There also was no difference in cognitive function scores when the data were analyzed according to whether the patient had ever undergone bypass surgery (P=.59).Long-term cognitive function is similar after coronary bypass surgery and coronary angioplasty in the majority of patients.

Abstract

Some randomized clinical trials of amiodarone therapy to prevent sudden cardiac death have had positive results and others have had negative results, but all were relatively small. This meta-analysis aimed to pool all trials to assess the effect of amiodarone on mortality and the impact of differences in patient population and study design on trial outcomes.Fifteen randomized trials were identified, and outcome measures were combined by use of a random effects model. The effect of patient population and study design on total mortality was assessed by use of a hierarchical Bayes model. Amiodarone reduced total mortality by 19% (confidence limits, 6% to 31%; P

Abstract

Serial antiarrhythmic drug testing guided by Holter monitoring and electrophysiologic study had similar clinical outcomes in the Electrophysiologic Study versus Electrocardiographic Monitoring (ESVEM) trial, while patients treated with sotalol had improved outcomes. The purpose of this study was to compare long-term cost-effectiveness of these management alternatives.Patients in the ESVEM trial were linked to computerized files of either the Health Care Finance Administration or the Department of Veterans Affairs. Total hospital costs and survival time over five year follow-up were measured using actuarial methods, and cost-effectiveness was calculated.Patients randomized to therapy guided by electrophysiologic study had more hospital admissions, higher costs, and a cost-effectiveness ratio of $162,500 per life year added compared with therapy guided by Holter monitoring. Patients randomized to sotalol had fewer hospitalizations, lower costs, and better survival than patients randomized to other drugs, and sotalol was a dominant strategy in the cost-effectiveness analysis. Patients for whom an effective drug was found had fewer hospital admissions, lower costs, and longer survival. These findings were robust in sensitivity analyses and in bootstrap replications.Serial drug testing guided by electrophysiologic study had an unfavorable cost-effectiveness ratio relative to Holter monitoring, while sotalol was cost-effective relative to other antiarrhythmic drugs.

Abstract

Randomized trials comparing coronary angioplasty with bypass surgery in patients with multivessel coronary disease have shown no significant differences in overall rates of death and myocardial infarction. We compared quality of life, employment, and medical care costs during five years of follow-up among patients treated with angioplasty or bypass surgery.A total of 934 of the 1829 patients enrolled in the randomized Bypass Angioplasty Revascularization Investigation participated in this study. Detailed data on quality of life were collected annually, and economic data were collected quarterly.During the first three years of follow-up, functional-status scores on the Duke Activity Status Index, which measures the ability to perform common activities of daily living, improved more in patients assigned to surgery than in those assigned to angioplasty (P<0.05). Other measures of quality of life improved equally in both groups throughout the follow-up period. Patients in the angioplasty group returned to work five weeks sooner than did patients in the surgery group (P<0.001). The initial mean cost of angioplasty was 65 percent that of surgery ($21,113 vs. $32,347, P<0.001), but after five years the total medical cost of angioplasty was 95 percent that of surgery ($56,225 vs. $58,889), a difference of $2,664 (P = 0.047). The five-year cost of angioplasty was significantly lower than that of surgery among patients with two-vessel disease ($52,930 vs. $58,498, P<0.05), but not among patients with three-vessel disease ($60,918 vs. $59,430). After five years of follow-up, surgery had an overall cost-effectiveness ratio of $26,117 per year of life added, but unacceptable ratios of $100,000 or more per year of life added could not be excluded (P=0.13). Surgery appeared particularly cost effective in treating diabetic patients because of their significantly improved survival.In patients with multivessel coronary disease, coronary-artery bypass surgery is associated with a better quality of life for three years than coronary angioplasty, after the initial morbidity caused by the procedure. Coronary angioplasty has a lower five-year cost than bypass surgery only in patients with two-vessel coronary disease.

Abstract

Implantable cardioverter defibrillators (ICDs) are remarkably effective in terminating ventricular arrhythmias, but they are expensive and the extent to which they extend life is unknown. The marginal cost-effectiveness of ICDs relative to amiodarone has not been clearly established.To compare the cost-effectiveness of a third-generation implantable ICD with that of empirical amiodarone treatment for preventing sudden cardiac death in patients at high or intermediate risk.A Markov model was used to evaluate health and economic outcomes of patients who received an ICD, amiodarone, or a sequential regimen that reserved ICD for patients who had an arrhythmia during amiodarone treatment.Life-years gained, quality-adjusted life-years gained, costs, and marginal cost-effectiveness.For the base-case analysis, it was assumed that treatment with an ICD would reduce the total mortality rate by 20% to 40% at 1 year compared with amiodarone and that the ICD generator would be replaced every 4 years. In high-risk patients, if an ICD reduces total mortality by 20%, patients who receive an ICD live for 4.18 quality-adjusted life-years and have a lifetime expenditure of $88,400. Patients receiving amiodarone live for 3.68 quality-adjusted life-years and have a lifetime expenditure of $51,000. Marginal cost-effectiveness of an ICD relative to amiodarone is $74,400 per quality-adjusted life-year saved. If an ICD reduces mortality by 40%, the cost-effectiveness of ICD use is $37,300 per quality-adjusted life-year saved. Both choice of therapy (an ICD or amiodarone) and the cost-effectiveness ratio are sensitive to assumptions about quality of life.Use of an ICD will cost more than $50,000 per quality-adjusted life-year gained unless it reduces all-cause mortality by 30% or more relative to amiodarone. Current evidence does not definitively support or exclude a benefit of this magnitude, but ongoing randomized trials have sufficient statistical power to do so.

Abstract

Several relatively small randomized trials have shown that primary angioplasty results in a better short-term outcome than thrombolytic therapy in patients with acute myocardial infarction. These results, however, have not been duplicated other than in investigational trials.We compared mortality during hospitalization and long-term mortality, as well as the use of resources, among 1050 patients in a primary-angioplasty group and 2095 patients in a thrombolytic-therapy group. Patients were selected from the Myocardial Infarction Triage and Intervention Project Registry cohort of 12,331 consecutive patients admitted with acute myocardial infarction to 19 Seattle hospitals between 1988 and 1994. Because of the potential for selection bias, several subgroup analyses were performed that included patients eligible for thrombolysis, high-risk patients, and patients in the primary-angioplasty group who were treated at hospitals with high volumes of angioplasty.There was no significant difference in mortality during hospitalization or long-term follow-up between patients in the thrombolytic-therapy group and those in the primary-angioplasty group (mortality during hospitalization, 5.6 percent and 5.5 percent, respectively; P=0.93; adjusted hazard ratio for the risk of death within three years after primary angioplasty, 0.95; 95 percent confidence interval, 0.8 to 1.2). There was also no significant difference in mortality between high-risk subgroups of patients in the two treatment groups. The rates of procedures and costs were lower among patients in the thrombolytic-therapy group both at the time of hospital discharge and after three years of follow-up (30 percent fewer coronary angiograms, 15 percent fewer coronary angioplasties, and 13 percent lower costs after three years of follow-up).In a community setting, we observed no benefit in terms of either mortality or the use of resources with a strategy of primary angioplasty rather than thrombolytic therapy in a large cohort of patients with acute myocardial infarction.

Abstract

We performed a meta-analysis of randomized trials that compared percutaneous transluminal coronary angioplasty (PTCA) with coronary artery bypass graft (CABG) surgery in patients with multivessel coronary artery disease. The outcomes of death, combined death, and nonfatal myocardial infarction (MI), repeat revascularization, and freedom from angina were analyzed. The overall risk of death and nonfatal MI was not different over a follow-up of 1 to 3 years (CABG:PTCA odds ratio [OR] 1.03, 95% confidence interval 0.81 to 1.32, p = 0.81). Patients randomized to CABG tended to have a higher risk of death or MI in the early, periprocedural period (OR 1.33, p = 0.091), but a lower risk in subsequent follow-up (OR 0.74, p = 0.093). CABG patients were much less likely to undergo another revascularization procedure (p < 0.00001), and were more likely to be angina free (OR 1.57, p < 0.00001). Thus, CABG and PTCA patients have similar overall risks of death and nonfatal MI at 1 to 3 years of follow-up, but relative risk differences in mortality of up to 25% cannot be excluded. CABG patients have significantly less angina and less repeat revascularization than PTCA patients.

Abstract

Treatment of acute myocardial infarction differs between the United States and Canada, but the reasons for these practice pattern differences remain elusive. To investigate whether physician beliefs and access to procedures account for these differences in the treatment of acute myocardial infarction, a random sample of physicians involved in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries trial in the United States (n = 332) and Canada (n = 200) was surveyed. We found that American physicians recommend coronary angiography after uncomplicated infarction significantly more (median: 7 versus 3 of 11 possible indications, P = 0.0001). Coronary angiography, angioplasty, and bypass surgery were available in-hospital to more American than Canadian physicians (77% versus 41%), and the reported waiting period for cardiac procedures in a stable patient was longer in Canada (angiography: 28 versus 1.5 days; angioplasty: 30 versus 2 days; bypass surgery: 84 versus 3 days, all P < 0.001). More American than Canadian physicians were cardiologists (88% versus 74%), and more were interventional cardiologists (61% versus 26%). American physicians more highly rated the importance of patient requests, malpractice, and insurance coverage, whereas Canadians more highly rated availability of cardiac procedures as influencing clinical decisions. After statistical adjustment for these factors, however, Americans remained significantly more likely to recommend coronary angiography.

Abstract

Patients with acute myocardial infarction who were treated with accelerated tissue plasminogen activator (t-PA) (given over a period of 1 1/2 hours rather than the conventional 3 hours, and with two thirds of the dose given in the first 30 minutes) had a 30-day mortality that was 15 percent lower than that of patients treated with streptokinase in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) study. This was equivalent to an absolute decrease of 1 percent in 30-day mortality. We sought to assess whether the use of t-PA, as compared with streptokinase, is cost effective.Our primary, or base-case, analysis of cost effectiveness used data from the GUSTO study and life expectancy projected on the basis of the records of survivors of myocardial infarction in the Duke Cardiovascular Disease Database. In the primary analysis, we assumed that there were no additional treatment costs due to the use of t-PA after the first year and that the comparative survival benefit of t-PA was still evident one year after enrollment.One year after enrollment, patients who received t-PA had both higher costs ($2,845) and a higher survival rate (an increase of 1.1 percent, or 11 per 1000 patients treated) than streptokinase-treated patients. On the basis of the projected life expectancy of each treatment group, the incremental cost-effectiveness ratio--with both future costs and benefits discounted at 5 percent per year--was $32,678 per year of life saved. The use of t-PA was least cost effective in younger patients and most cost effective in older patients. At all ages, the use of t-PA in patients with anterior infarctions yielded more favorable cost-effectiveness values. In our secondary analyses, the cost-effectiveness values were most sensitive to a lowering of the projected long-term survival benefits of t-PA and to moderate or greater increases in the projected medical costs for patients in the t-PA group after the first year. In contrast, our results were not sensitive to even very unfavorable assumptions about the additional costs associated with the higher rate of disabling stroke that was noted in patients treated with t-PA in the GUSTO study.The cost effectiveness of treatment with accelerated t-PA rather than streptokinase compares favorably with that of other therapies whose added medical benefit for dollars spent is judged by society to be worthwhile.

Abstract

Randomized trials of coronary angioplasty and bypass surgery have hypothesized that these procedures will have equivalent long-term rates of death and myocardial infarction. Functional status, quality of life, employment, and healthcare cost will therefore be critical measures of the efficacy of these alternative revascularization procedures. Patients at 7 sites in the Bypass Angioplasty Revascularization Investigation (BARI) were enrolled in an ancillary Study of Economics and Quality of Life (SEQOL). Physical function was assessed by the Duke Activity Status Index and emotional status by the Mental Health Inventory. Employment patterns and health care utilization were also measured at study entry and at 3-month intervals in follow-up. The 934 patients enrolled in SEQOL were similar to the 895 remaining BARI randomized patients. Most patients (63%) aged < or = 64 years were working, and almost all working patients (96%) intended to return to work. Patients aged > or = 65 years had lower household incomes but better health insurance coverage. Overall health ratings were significantly correlated with both physical and emotional status (p < 0.001). Patients enrolled in SEQOL are representative of the overall BARI population. Data collected in SEQOL will provide a detailed picture of the physical, emotional, and economic well-being after coronary angioplasty and bypass surgery.

Abstract

Patients randomized to either serial electrophysiological testing (EPS) or serial Holter monitoring (HM) to guide antiarrhythmic therapy for life-threatening ventricular arrhythmias had equivalent rates of mortality and arrhythmia recurrence in the ESVEM study. This report analyzes the effects of EPS, HM, and clinical factors on the charges for initial evaluation and management of patients with life-threatening ventricular arrhythmias.Ten of 14 clinical centers participating in ESVEM provided bills from the initial hospitalization for randomized patients. Predictors of charges (1991 dollars) were analyzed by linear regression after logarithmic transformation. Initial hospital charge data were obtained for 286 patients randomized in ESVEM (88% of patients eligible for this substudy, 59% of all ESVEM patients). Patients with charge data were somewhat more likely to be older, to be female, and to have failed previous antiarrhythmic drug therapy at study entry and were less likely to have a drug predicted effective after randomization. Mean overall hospital charges were $35,986 (SD, $32,628) with a median of $24,532 (interquartile range, $16,126 to $43,593). Prerandomization patient characteristics generally had insignificant effects on charges, with the exception of presentation with resuscitated sudden death (28% increase in charges, P = .01) and heart failure (26% increase in charges, P = .02). Patients randomized to EPS had higher mean charges for evaluation ($42,002 versus $29,970, P = .0015) as well as more drug trials (3.0 versus 2.1, P = .0001) and a longer hospital stay (19.6 versus 13.9 days, P = .0007). In a multivariate regression model, failure to find an effective drug (P = .0001), the number of drug trials (P = .0001), and resuscitated sudden death as the presenting arrhythmia (P = .0001) were the only independent predictors of higher initial charges.(1) Initial hospital charges are significantly higher for EPS-guided than HM-guided therapy. (2) The higher charges for EPS-guided therapy were due to a greater number of drug trials and a lower probability of finding an effective drug. (3) Failure to find an effective drug, a larger number of drug trials, and a history of resuscitated sudden death independently predict higher charges.

DIFFERENCES IN THE TREATMENT OF MYOCARDIAL-INFARCTION IN THE UNITED-STATES AND CANADA - A COMPARISON OF 2 UNIVERSITY HOSPITALSARCHIVES OF INTERNAL MEDICINEPilote, L., Racine, N., Hlatky, M. A.1994; 154 (10): 1090-1096

Abstract

To compare practice patterns and clinical outcomes for a costly yet common condition, acute myocardial infarction.Retrospective cohort study in two university hospitals (Stanford [Calif] University and McGill University, Montreal, Quebec) and a patient survey.All consecutive patients (n = 518) treated for acute myocardial infarction in the coronary care unit of those two hospitals over 2 years.Rates of diagnostic and therapeutic procedures, mortality, reinfarction, and level of functional status (by chart review and patient survey).Demographic and clinical characteristics were similar for the two groups. Noninvasive tests were more common at McGill (exercise tests, 56% vs 20%; tests of left ventricular function, 86% vs 59%; P < .0001 for both). In contrast, invasive procedures were more common at Stanford (angiography, 55% vs 34%; angioplasty, 30% vs 13%; and bypass surgery, 10% vs 4%; P < .0001). At a median follow-up of 20 months, reinfarction and mortality rates were similar at Stanford and McGill (13% vs 8% and 28% vs 27%, respectively; P > .05 for both). In contrast, the angina rate was slightly lower at Stanford (33% vs 40%; P = .15), and the functional status of Stanford patients was better than that of McGill patients (mean Duke Activity Status Index score, 28.8 and 22.9, respectively; P = .006). This functional status difference persisted after adjustment for differences in clinical factors, including coronary revascularization.The aggressive treatment of the American patients with myocardial infarction did not improve reinfarction and mortality rates compared with the conservative treatment of the Canadian patients. The superior functional status of the American patients merits further investigation.

Abstract

To compare return-to-work rates after coronary angioplasty, coronary bypass surgery, and medical therapy in patients with coronary disease.Prospective cohort study.Tertiary care referral center.Between March 1986 and June 1990, we enrolled 1252 patients who were younger than 65 years, who had not had previous coronary revascularization, and who were employed. All patients were followed for 1 year.One-year employment status.After 1 year, 84% of patients who had coronary angioplasty were still working compared with 79% of patients who had bypass surgery and with 76% of patients who received medicine. After adjusting for the more favorable baseline characteristics of patients who had angioplasty (less severe coronary artery disease, better left ventricular function, and less functional impairment), however, no significant differences were noted in 1-year employment rates among the three groups. These adjusted 1-year return-to-work rates were 84% for angioplasty, 80% for surgery, and 79% for medicine (P > 0.05). In a random subset of 72 patients, 23 patients who had angioplasty returned to work after a median of 18 days (mean, 27 days) compared with 54 days (mean, 67 days) for 24 patients having bypass surgery and with 14 days (mean, 45 days) for 25 patients receiving medicine (P = 0.002).Patients who had coronary angioplasty were able to return to work earlier than those who had bypass surgery, but by 1 year no significant difference was noted in employment rates. Neither revascularization strategy improved employment rates when compared with initial treatment using medical therapy.

Abstract

The cost of treating disease depends on patient characteristics, but standard tools for analyzing the clinical predictors of cost have deficiencies. To explore whether survival analysis techniques might overcome some of these deficiencies in the analysis of cost data, we compared ordinary least square (OLS) linear regression (with and without transformation of the data) and binary logistic regression with two survival models: the Cox proportional hazards model and a parametric model assuming a Weibull distribution. Each model was applied to data from 155 patients undergoing coronary artery bypass grafting. We examined the effects of age, sex, ejection fraction, unstable angina, and number of diseased vessels on univariable and multivariable predictions of costs. The significant univariable predictors of cost were consistent in all models: ejection fraction was significant in all five models, and age and number of diseased vessels were each significant in all but the OLS model, while sex and angina type were significant in none of the models. The significant multivariable predictors of cost, however, differed according to model: ejection fraction was a significant multivariable predictor of cost in all five models, age was significant in three models, and number of diseased vessels was significant in one model. All five models were also used to predict the costs for an average patient undergoing surgery. The Cox model provided the most accurate predictions of mean cost, median cost, and the proportion of patients with high cost. This study shows: (1) lower ejection fraction and older age are independent clinical predictors of increased cost of CABG, and (2) the Cox proportional hazards model shows considerable promise for the analysis of the impact of clinical factors upon cost.

Abstract

Work disability is common in patients with coronary artery disease and adversely affects both economic well-being and quality of life. The purpose of this study was to construct a model to predict premature departure from the work force of patients with coronary disease and to validate this model prospectively in an independent cohort of patients.We enrolled 1,252 coronary disease patients referred for diagnostic cardiac catheterization who were less than age 65, employed, and without prior coronary angioplasty or coronary bypass surgery. Medical, functional, psychological, economic, and job-related variables were measured at the time of baseline diagnostic cardiac catheterization, and all patients were followed for 1 year. Three hundred twelve patients underwent percutaneous transluminal coronary angioplasty (PTCA) within 60 days of catheterization, and 449 had coronary artery bypass graft surgery (CABG) within 60 days of catheterization. The remaining 491 patients were treated with initial medical therapy. Logistic regression was used to develop a multivariable model for predicting 1-year work status in the training sample patients (872 patients enrolled between March 1986 and February 1989). This model was then validated in the independent prospective test sample (380 patients enrolled between March 1989 and June 1990). Eight factors were independent predictors of departure from the work force: lower initial functional status (as assessed by the Duke Activity Status Index), followed by older age, black race, presence of congestive heart failure, lower education level, presence of extracardiac vascular disease, poorer psychological status, and lower job classification. Standard clinical variables provided only 20% of the total predictive information available from the model about follow-up work outcomes, whereas functional measures provided 27%, and demographic and socioeconomic measures provided 45%. In the test sample, the area under the receiver operating characteristic curve for the model predictions was 0.74, compared with 0.80 in the training sample, and model predictions agreed well with observed prevalences of return to work. After adjustment for baseline imbalances, there was no significant difference in 1-year return-to-work rates among the patients receiving initial PTCA or CABG therapy versus initial medical therapy.Patients with coronary disease who are at high risk for premature departure from the work force can be accurately identified from a combination of medical and nonmedical risk factors. The model developed in this study provides a tool to identify patients at high risk for premature loss from the work force. Such patients may benefit from special multidimensional intervention programs designed to preserve work status. Our data show that revascularization with either PTCA or CABG is not, by itself, sufficient to accomplish this goal.

Abstract

The treadmill exercise test identifies patients with different degrees of risk of death from cardiovascular events. We devised a prognostic score, based on the results of treadmill exercise testing, that accurately predicts outcome among inpatients referred for cardiac catheterization. This study was designed to determine whether this score could also accurately predict prognosis in unselected outpatients.We prospectively studied 613 consecutive outpatients with suspected coronary disease who were referred for exercise testing between 1983 and 1985. Follow-up was 98 percent complete at four years. The treadmill score was calculated as follows: duration of exercise in minutes--(5 x the maximal ST-segment deviation during or after exercise, in millimeters)--(4 x the treadmill angina index). The numerical treadmill angina index was 0 for no angina, 1 for nonlimiting angina, and 2 for exercise-limiting angina. Treadmill scores ranged from -25 (indicating the highest risk) to +15 (indicating the lowest risk).Predicted outcomes for the outpatients, based on their treadmill scores, agreed closely with the observed outcomes. The score accurately separated patients who subsequently died from those who lived for four years (area under the receiver-operating-characteristic curve = 0.849). The treadmill score was a better discriminator than the clinical data and was even more useful for outpatients than it had been for inpatients. Approximately two thirds of the outpatients had treadmill scores indicating low risk (greater than or equal to +5), reflecting longer exercise times and little or no ST-segment deviation, and their four-year survival rate was 99 percent (average annual mortality rate, 0.25 percent). Four percent of the outpatients had scores indicating high risk (less than -10), reflecting shorter exercise times and more severe ST-segment deviation; their four-year survival rate was 79 percent (average annual mortality rate, 5 percent).The treadmill score is a useful and valid tool that can help clinicians determine prognosis and decide whether to refer outpatients with suspected coronary disease for cardiac catheterization. In this study, it was a better predictor of outcome than the clinical assessment.

USING DATABASES TO EVALUATE THERAPY3RD BIENNIAL REGENSTRIEF CONF ON METHODS FOR USING LARGE DATABASES IN HEALTH CARE RESEARCH : PROBLEMS AND PROMISESHlatky, M. A.JOHN WILEY & SONS LTD.1991: 647–52

Abstract

Clinical and administrative databases are increasingly used for clinical research. Descriptive studies and analyses of prognostic factors are established research uses of databases, but using them to compare therapies remains controversial. Such comparisons may be possible when a validated model of prognosis can account for the effect of clinically recognized variables on outcome. Models meeting these criteria have been developed using the Duke Cardiovascular Disease Database. They were applied to compare medical therapy to surgical therapy for coronary artery disease. Predictions from these models agreed well with the results of the three major randomized trials of bypass surgery versus medical therapy. These findings indicate that when data is reliable and understanding of factors affecting prognosis is good, researchers can use statistical techniques to minimize the bias due to non-random treatment assignment. Carefully performed analyses of observational clinical data can complement and extend randomized studies.

Abstract

Although there is intense interest in the cost-saving potential of therapeutic alternatives, most studies have analyzed hospital charges rather than actual economic costs. To analyze cost differences rigorously, we studied 115 patients undergoing initial elective angioplasty (percutaneous transluminal coronary angioplasty, PTCA) and 274 patients undergoing initial elective surgery (coronary artery bypass graft surgery, CABG). Detailed resource consumption profiles were constructed and used to estimate the cost savings from switching a patient from CABG to PTCA. Four cost-accounting methods were used in the analysis; each method made different assumptions about the costs that would vary and the costs that would be fixed according to the number of procedures performed. The variable costs in the four methods were the 1) cost of supplies, 2) cost of personnel and supplies, 3) average direct costs, and 4) average direct costs plus allocated hospital overhead. The mean hospital charges for CABG patients were $19,644 versus $9,556 for PTCA patients (p less than 0.0001). The estimated cost difference between CABG and PTCA was substantially less than the $10,088 difference in charges, however, with net savings of 19%, 46%, 53%, and 78% of charges using cost-accounting methods 1-4, respectively. Thus, although the initial hospital charges for PTCA are significantly less than for CABG, the actual economic cost savings may be significantly overestimated by the use of hospital charge data.

Abstract

To evaluate the effectiveness and cost of low osmolarity, nonionic contrast agents for cardiac angiography, 443 patients were randomized to receive either iopamidol or diatrizoate. All adverse events that occurred within 24 h of the procedure were recorded prospectively by study personnel and classified according to previously determined criteria. Major events were defined as life threatening or requiring a procedure to treat, or both. Costs of the catheterization procedure, pharmacy, hospital laboratory and treatment of adverse events were determined on the basis of actual resource use. A total of 20 patients (8.5%) had major and 143 (61%) had minor adverse events with diatrizoate use; 10 patients (4.8%) had major and 53 (25%) had minor adverse events with iopamidol (p = 0.12 for major events; p less than 0.001 for total events). Most adverse events were treated fairly easily and inexpensively. The median overall cost was $186 higher for patients after iopamidol use compared with diatrizoate (p less than 0.0001), but all costs except the cost of the contrast agent were not significantly different between the two groups. Thus, patients who received iopamidol for cardiac angiography had a significantly lower rate of adverse events than those who received diatrizoate, but this difference was achieved at a considerably high overall cost.

Abstract

This study examined the relation between the risk of cardiac rupture and the timing of thrombolytic therapy for acute myocardial infarction. To test the hypothesis that cardiac rupture is prevented by early thrombolytic therapy but is promoted by late treatment, randomized controlled trials of thrombolytic agents for myocardial infarction were pooled. A logistic regression model including 58 cases of cardiac rupture among 1,638 patients from four trials showed that the odds ratio (treated/control) of cardiac rupture was directly correlated with time to treatment (p = 0.01); at 7 h, the odds ratio was 0.4 (95% confidence limits 0.17 to 0.93); at 11 h, it was 0.93 (0.53 to 1.60) and at 17 h, it was 3.21 (1.10 to 10.1). Analysis of data from the Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico (GISSI) trial independently confirmed the relation between time to thrombolytic therapy and risk of cardiac rupture (p = 0.03). Analysis of 4,692 deaths in 44,346 patients demonstrated that the odds ratio of death was also directly correlated with time to treatment (p = 0.006); at 3 h, the odds ratio for death was 0.72 (0.67 to 0.77); at 14 h, it was 0.88 (0.77 to 1.00) and at 21 h, it was 1 (0.82 to 1.37). Thrombolytic therapy early after acute myocardial infarction improves survival and decreases the risk of cardiac rupture. Late administration of thrombolytic therapy also appears to improve survival but may increase the risk of cardiac rupture.

Abstract

To determine the feasibility and cost-saving potential of substituting outpatient for inpatient cardiac catheterization, 986 consecutive procedures were studied at a large referral hospital. Patients were classified prospectively as to their eligibility for outpatient cardiac catheterization according to published guidelines. Resource consumption was recorded, and cost savings were then calculated by analyzing the specific supply and personnel costs that could change as a result of inpatient versus outpatient status. Of the total of 986 patients who underwent diagnostic catheterization, 240 (24%) were outpatients, 279 (28%) were inpatients but had no exclusion criteria for outpatient catheterization and 467 (47%) were inpatients who had one or more exclusions for outpatient catheterization. The most common reasons for exclusion from outpatient catheterization were congestive heart failure (22%), unstable angina (15%), noncoronary heart disease (14%), recent myocardial infarction (11%) and severe noncardiac disease (9%). Inpatients with no exclusions for the outpatient procedure tended to be sicker than outpatients because they were older (p = 0.002), had a lower ejection fraction (p = 0.009) and had more triple vessel coronary artery disease (p less than 0.0001). The cost of the catheterization procedure itself was not different between inpatients and outpatients. Laboratory testing was more frequent among inpatients, however, and "room and board" costs were significantly higher. Although the difference in hospital charges for inpatients and outpatients was $580, a rigorous analysis indicated that the potential cost savings was only 38% of this amount, or $218 per eligible patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract

Clinical decision making is under increased scrutiny due to concerns about the cost and quality of medical care. Variability in physician decision making is common, in part because of deficiencies in the knowledge base, but also due to the difference in physicians' approaches to clinical problem solving. Evaluation of patient prognosis is a critical factor in the selection of therapy, and careful attention to methodology is essential to provide reliable information. Randomized controlled clinical trials provide the most solid basis for the establishment of broad therapeutic principles. Because randomized studies cannot be performed to address every question, observational studies will continue to play a complementary role in the evaluation of therapy. Randomized studies in progress, meta analyses of existing data, and increased use of administrative and collaborative clinical data bases will improve the knowledge base for decision making in the future.

Abstract

To elucidate the factors associated with improved survival following coronary artery bypass surgery, we studied 5809 patients receiving medical or surgical therapy for coronary artery disease. Three factors were associated with a significant surgical survival benefit: more severe coronary disease, a worse prognosis with medical therapy, and a more recent operative date. Patients with more extensive coronary obstruction had the greatest improvement in survival. Patients with a poor prognosis because of factors such as older age, severe angina, or left ventricular dysfunction had a reduction in risk that was proportionate to their overall risk on medical therapy. Survival with surgery progressively improved over the study period and by 1984 surgery was significantly better than medical therapy for most patient subgroups. Thus, contemporary coronary revascularization is associated with improved longevity in many patients with ischemic heart disease, especially in those with adverse prognostic indicators.

Abstract

Acutely ill patients with myocardial infarction may require immediate cardiac catheterization and coronary angioplasty to achieve myocardial reperfusion. To determine the feasibility of using general anesthesia under these circumstances, a randomized clinical trial was performed. Of 50 patients, 25 received anesthesia and 25 receive intravenous sedation. There were transient increases in heart rate and blood pressure after tracheal intubation in the anesthetized patients, followed by significant and sustained decreases below baseline values once steady state anesthesia was attained. Arterial oxygenation was significantly improved in anesthetized patients. There were no serious complications due to anesthesia, but the small sample size limited the power of the study to detect differences in morbidity or mortality. Patients strongly preferred anesthesia. These results show that general anesthesia is feasible in patients undergoing interventional cardiac catheterization during acute myocardial infarction, when pain, anxiety or agitation do not respond adequately to conventional measures.

Abstract

Little is known about how different types of physicians use laboratory procedures in the management of outpatients with congestive heart failure. We therefore analyzed data from a national survey of randomly selected general practitioners, internists, and cardiologists to assess their management of outpatients with New York Heart Association class II congestive heart failure. Most of the 2704 respondents (90%) scheduled office visits between two and four months apart. Body weight, serum electrolytes, and chest roentgenograms were followed regularly by 98% or more of respondents, at median intervals of one to two months, three to five months, and 12 to 17 months, respectively. Serum digoxin levels in patients taking digoxin were followed by 90% of respondents at a median interval of 12 months. Echocardiography, radionuclide ventriculography, and exercise testing were used by fewer respondents (81%, 61%, and 61%, respectively), each at a median interval of 18 months or longer. Cardiologists were significantly more likely to follow patients using either echocardiography, radionuclide ventriculography, or exercise testing. The estimated yearly cost of following a class II congestive heart failure outpatient varied nearly fourfold from the lowest quartile of physicians ($303) to the highest ($1167). Cardiologists were disproportionately represented among the high-cost users. In addition, physicians who were younger or who practiced in an urban setting were significantly more likely to be high-cost users. Thus, simple laboratory tests were used most frequently to follow patients with heart failure, but differences in use of more expensive tests led to large differences in cost. Test use for similar patients is affected by characteristics of both the physician and practice setting.

Abstract

Experimental studies have suggested that nonionic contrast agents are less nephrotoxic than ionic contrast agents. To examine the relative nephrotoxicity of the two types of agents, we randomly assigned 443 patients to receive either iopamidol (nonionic) or diatrizoate (ionic) for cardiac catheterization. The patients were stratified into low-risk (n = 283) or high-risk (n = 160) groups, on the basis of the presence of diabetes mellitus, heart failure, or preexisting renal insufficiency (base-line serum creatinine level, greater than 133 mumol per liter). Serum and urine analyses were performed at base line and 24 and 48 hours after the infusion of contrast material. Nephrotoxicity was defined as an increase in the serum creatinine level within 48 hours of at least 44 mumol per liter. The median maximal rise in the serum creatinine level was 18 mumol per liter in both the diatrizoate group (n = 235) and the iopamidol group (n = 208) (P not significant; power to detect a difference greater than 9 mumol per liter, greater than 90 percent). Creatinine levels increased by at least 44 mumol per liter (0.5 mg per deciliter) in 10.2 percent of the patients receiving diatrizoate and 8.2 percent of the patients receiving iopamidol (P not significant). Among the high-risk patients, creatinine levels increased by at least 44 mumol per liter in 17 percent of the patients in the diatrizoate group, as compared with 15 percent of the patients in the iopamidol group (P not significant). We were unable to demonstrate a difference in the incidence of nephrotoxicity between patients receiving a non-ionic contrast agent and those receiving an ionic contrast agent.

Abstract

To determine the incidence of cardiovascular and renal toxicity of a nonionic contrast agent when used for cardiac catheterization, and to assess the value of electrolytes and urinalysis results as predictors of nephropathy induced by a contrast agent.Nonrandomized trial using a criterion standard and a cohort analytic study with a 48-hour follow-up.Referral-based university hospital.Convenience sample of patients having diagnostic cardiac catheterization. Renal function and clinical status were evaluated at baseline in 1,144 patients; at 24 hours in 1,077 (94%); and at 48 hours in 663 (57%).After patients received saline for hydration, coronary angiography and left ventriculography were done with iopamidol (average dose, 203 +/- 56 cc).The definite and possible incidence of major acute cardiovascular complications from nonionic contrast media was 0.2% and 0.7%, respectively. The mean serum creatinine level increased 11.5 mumol/L from baseline at 24 hours (P less than 0.0001) and 16.8 mumol/L from baseline at 48 hours (P less than 0.0001). Results in a randomly selected training sample were studied to determine predictors of a rise in serum creatinine of 44.2 mumol/L or more. The baseline serum creatinine level and age were significant predictors of renal injury, but hypertension, diabetes mellitus, congestive heart failure, vascular disease, the volume of contrast agent injected or baseline values of urinary variables did not predict nephrotoxicity. In an independent validation sample, only the baseline serum creatinine level was confirmed as a predictor of nephrotoxicity, whereas age was not. A model that predicted contrast-induced nephropathy by the serum creatinine level showed an exponential increase in the risk for nephrotoxicity if the baseline level was 106.1 mumol/L or higher.Patients have a small but significant rise in serum creatinine after cardiac catheterization with a nonionic contrast agent. Baseline renal insufficiency is the only confirmed predictor of nonionic contrast-induced nephrotoxicity.

Abstract

A national survey of 1,065 physicians was carried out to document current use of thrombolytic therapy for acute myocardial infarction (AMI). In early 1987, thrombolytic therapy was used by 66% of respondents. Among those who used thrombolytic therapy, 92% used streptokinase, 13% used tissue-type plasminogen activator and 3% used urokinase. Most (72%) used intravenous administration exclusively and only 5% used intracoronary administration exclusively. Despite widespread acceptance of thrombolytic therapy, most physicians gave it to less than 25% of their patients. Duration of symptoms was rated as the single most important factor affecting the decision to use thrombolytic therapy; 45% had a time limit of less than 4 hours and 85% had a time limit of less than 6 hours. Complications of AMI and electrocardiographic findings were factors also considered in the decision to give this therapy. A physician's adoption of thrombolytic therapy was significantly associated with several characteristics: specialty type, number of AMI patients treated, physician age and access to cardiac catheterization. In addition, physicians using thrombolytic therapy had a significantly different use of medications and laboratory tests for all patients with AMI. This survey documents rapid acceptance of thrombolytic therapy for AMI, particularly in patients with short duration of symptoms or evidence of high risk.

Abstract

To document current management of uncomplicated acute myocardial infarction (AMI), a national survey of 1,065 physicians was performed. Items from previous surveys in 1970 and 1979 were included to permit analysis of time trends in management. Median hospital stay dropped from 21 days in 1970 to 9 days in 1987. Use of beta blockers and aspirin doubled between 1979 and 1987, while use of anticoagulation and sulfinpyrazone dropped 4- to 10-fold. In 1987, coronary angiography was used commonly, especially in younger patients or those with either a non-Q-wave AMI, intravenous thrombolytic therapy or a positive exercise test. These findings document the increasingly aggressive approach to the management of patients with uncomplicated AMI.

Abstract

Seven hundred seventy-five consecutive patients with symptoms suggestive of acute myocardial infarction (AMI) who were admitted to the cardiac care unit from the emergency room were studied; 107 had normal electrocardiographic findings and 73 had only minimal nonspecific changes. AMI subsequently evolved in 11 patients (10%) with normal electrocardiographic findings and in 6 (8%) with minimal changes, compared with 245 (41%) with frankly abnormal emergency room findings. Only 1 (1%; 95% confidence limits 0.02 to 5%) and 4 (6%; 95% confidence limits 2 to 15%) of those with normal and nonspecific initial electrocardiographic findings, respectively, had a complication for which they potentially benefited from intensive care unit intervention, although many patients received prophylactic therapy. Thus, the initial emergency room electrocardiogram can effectively separate patients into high- and low-risk groups for AMI and serious complications. Admission to a monitored intermediate care ward may be an acceptable practice in patients with chest pain and a normal or minimally changed initial electrocardiogram.

Abstract

To determine the prognostic value of the treadmill exercise test, we evaluated 2842 consecutive patients with chest pain who had both treadmill testing cardiac catheterization. The population was randomly divided into two equal-sized groups and the Cox regression model was used in one to form a treadmill score that was then validated in the other group. The final treadmill score was calculated as follows: exercise time--(5 X ST deviation)--(4 X treadmill angina index). Using this treadmill score, 13% of the patients were found to be at high risk; 53%, at moderate risk; and 34%, at low risk. The treadmill score added independent prognostic information to that provided by clinical data, coronary anatomy, and left ventricular ejection fraction: patients with three-vessel disease with a score of -11 or less had a 5-year survival rate of 67%, and those with a score of +7 or more had a 5-year survival rate of 93%. The treadmill score was useful for stratifying prognosis in patients with suspected coronary artery disease who were referred to us for catheterization, and may provide a useful adjunct to clinical decision making in the larger population of patients being evaluated for chest pain.

Abstract

To determine if patterns of ST depression or elevation during exercise testing provide reliable information about the location of an underlying coronary lesion, we studied 452 consecutive patients with one-vessel disease who underwent treadmill testing. Exercise ST changes were classified as elevation or depression and by lead groups involved. The ST depression occurred most commonly in leads V5 or V6 regardless of which coronary artery was involved. In contrast, anterior ST elevation indicated left anterior descending coronary disease in 93% of cases, and inferior ST elevation indicated a lesion in or proximal to the posterior descending artery in 86% of cases. Furthermore, anterior ST elevation in leads without diagnostic Q waves usually indicated a high-grade, often proximal, left anterior descending stenosis, whereas anterior ST elevation in leads with Q waves usually indicated a totally occluded left anterior descending coronary artery. Thus, ST elevation during exercise testing, although uncommon, is a reliable guide to the underlying coronary lesion, whereas ST depression is not.

Abstract

The clinical presentation and prognosis of 1,977 consecutive patients with normal coronary arteries or "insignificant" coronary artery disease (CAD) (no major epicardial artery with 75% or more luminal diameter narrowing) were examined. Compared with patients with significant CAD, these patients had a lower frequency of traditional cardiac risk factors and abnormalities on the rest and exercise electrocardiogram. Cardiac survival was 99% at 5 years of follow-up and 98% at 10 years for patients with normal or insignificantly narrowed coronary arteries. Patients with normal coronary arteries differed from those with insignificant CAD in their myocardial infarction free survival rate: 99% at 5 years and 98% at 10 years for patients with normal coronary arteries, compared with 97% at 5 years and 90% at 10 years for patients with insignificant CAD. A strong relation occurred between the amount of insignificant CAD and follow-up cardiac events (chi 2 = 21.5, p less than 0.0001). Cardiac risk factors were statistically related to the risk of follow-up cardiovascular events when considered alone (chi 2 = 4.93, p = 0.026), but this relation lost significance after adjusting for the effect of coronary anatomy. Patients in both groups continued to have cardiac symptoms that resulted in frequent hospitalizations, medication use and job disability. Almost 50% in any given year of follow-up could not perform activities of high metabolic equivalent requirement and 70% had continuing symptoms of chest discomfort. Although these patients are at low risk of death, many remain functionally impaired for years.

Abstract

This study identifies the medical, psychologic and social factors that independently affect employment in patients with coronary artery disease (CAD). At coronary angiography, extensive clinical, psychological and social profiles were collected on 814 men younger than 60 years with documented CAD. Clinical factors studied included measures of symptom severity, prior myocardial infarction, coronary anatomy and left ventricular function. Psychosocial factors studied included the Minnesota Multiphasic Personality Inventory (MMPI), Zung Depression and Anxiety Scales, a type A structured interview, Jenkins Activity Survey and measures of education and social support. Multiple logistic regression analyses were used to assess the relative strength of the relation between these different factors and the patients' employment status. Many single factors differed between the 204 men (25%) who were disabled and the 610 (75%) who were not. Disabled men were less educated but no different in age, marital status or number of dependents. Disabled men had lower ejection fractions and higher indexes of angina, previous myocardial infarction and coexisting vascular disease. Disabled men also were more depressed and anxious and had lower ego strength and higher hypochondriasis scores on the MMPI, but were no different in type A behavior. By multivariable analysis, the most significant (p less than 0.01) independent predictors of work disability were, in decreasing order of importance, low education level, history of myocardial infarction, high levels of depression and high levels of hypochondriasis. It is concluded that psychological and social factors are strongly related to work status in patients with CAD, and may be more important than medical factors.

Abstract

Exercise testing has proven value for the diagnosis of cardiac disorders in symptomatic patients and for the objective measurement of functional capacity. Use of exercise tests to screen for cardiac disease in asymptomatic persons remains controversial because of the low prevalence of disease in the population tested, the different characteristics of the test in asymptomatic persons, and the uncertain value of the information generated. This paper addresses the use of exercise testing to screen for coronary artery disease in asymptomatic persons. The principles underlying the use of screening tests will first be presented. The epidemiological evidence concerning screening exercise tests will then be reviewed, followed by the data concerning the prognosis and treatment of asymptomatic coronary disease. Finally, possible indications for screening exercise tests in specific occupations will be addressed.

Abstract

To study the mechanism and prognostic importance of precordial ST-segment depression during inferior acute myocardial infarction, 162 patients admitted during 1969 through 1982 were identified. Patients with ST depression in leads V1, V2 and V3 had significantly larger infarctions as assessed by a QRS scoring system. Hospital mortality was 4% (3 of 75) among patients without ST depression, and 13% (11 of 87) in patients with ST depression. The relation between the amount of ST depression and hospital mortality was significant (p less than 0.001 by logistic regression), and remained significant (p less than 0.003) after adjusting for other potentially prognostic factors. Among patients discharged from the hospital, the 5-year survival was 92% in those without precordial ST depression and 80% in those with precordial ST depression (p = 0.058 by the Cox model). Precordial ST-segment depression on the admission electrocardiogram during an inferior acute myocardial infarction indicates a larger infarction, predicts a higher hospital mortality and suggests a worse long-term prognosis after discharge.

Abstract

To evaluate the usefulness of the admission electrocardiogram, we prospectively studied 1410 patients admitted to a general medical service. The patients' history and physical examination were analyzed, and then the electrocardiogram was evaluated to determine whether it added new information. Fifty-two admission electrocardiograms added unique information; 31 established a new diagnosis, 28 of which changed management. Twenty-one electrocardiograms suggested a new diagnosis, 13 of which proved correct. Only age and a clinically evident cardiac abnormality predicted the yield of the admission electrocardiogram. Among patients with cardiac abnormalities, electrocardiogram yield was 8.5% in those 45 years or older and 2.5% in those younger. Among patients without cardiac abnormality, electrocardiogram yield was 1.0% overall and its cost-effectiveness was $24 000 per year of life saved. An admission electrocardiogram infrequently added new information to the clinical evaluation, but was useful when it did. Admission electrocardiograms are as cost-effective as many accepted medical practices.

Abstract

To permit comparison of percutaneous transluminal coronary angioplasty (PTCA) with conventional therapy, the clinical outcome was established in patients who would have been suitable candidates for PTCA but who presented before the technique was available. Coronary angiograms were reviewed of patients who met the following criteria: single-vessel disease with proximal subtotal coronary stenosis, chest pain of at least class II, and cardiac catheterization before 1981. Angiograms were evaluated according to established criteria for PTCA by an experienced angiographer. One hundred ten patients (2.1% of the patient population) were judged suitable for PTCA. Clinical and catheterization findings closely resembled those of patients in the national PTCA registry. Five years after catheterization, 97% of PTCA candidates treated medically were alive and 85% had not had myocardial infarction. Forty-six patients had coronary artery bypass surgery within 6 months of catheterization and 10 other patients had subsequent surgery. Five years after surgery, 91% were alive and 87% had not had myocardial infarction. At 6 months of follow-up, 78% of all patients had improved at least 1 functional class, and 86% of all patients working before catheterization were still employed. Functional capacity was well maintained during long-term follow-up (median 6.5 years, range 1.4 to 12.2). These data indicate that PTCA candidates have an excellent prognosis for survival, a low risk of infarction, and well-maintained functional capacity when revascularization is reserved for those with inadequate control of symptoms by medical therapy.

Abstract

Health maintenance organizations (HMOs) have lower than average medical care costs, but the reasons remain controversial. The diagnostic practices of cardiologists from an HMO, a university, and a community were therefore surveyed. First, cardiologists defined indications for coronary bypass surgery and then evaluated randomly selected case summaries of patients with chest pain. After review, the cardiologist rated the need for an exercise thallium scintiscan and for a coronary angiogram in each case. Community cardiologists had the broadest indications for bypass surgery. The HMO cardiologists chose thallium scintigraphy significantly less often than the other two types of cardiologists did. The HMO and university cardiologists both rated the need for coronary angiography significantly lower than did community cardiologists. Physicians in different practice settings therefore recommend costly diagnostic and therapeutic methods differently, even for identical patients.

Abstract

Probability analysis has provided insights into the use of diagnostic tests in coronary artery disease, and recent developments may permit clinical application of individual patients. To validate independently two available methods of probability calculation, their diagnostic accuracy was compared with that of cardiologists. Ninety-one cardiologists participated in the study; each evaluated the clinical summaries of eight randomly selected patients. For each patient, the cardiologist assessed the probability of coronary artery disease after reviewing the clinical history, physical examination and laboratory data, including complete results from a treadmill exercise test. The probability of coronary artery disease was also obtained for each patient, using the identical information, from two methods employing Bayes' rule: (1) from a published table of data based on the patient's age, sex, symptoms and degree of S-T segment change during exercise; and (2) from a computer program using the age, sex, risk factors, resting electrocardiogram and multiple exercise measurements. Diagnostic accuracy was assessed on a scale from 0 to 100 with the coronary angiogram as the diagnostic standard. The average diagnostic accuracy on this scale was: 80.2 for the cardiologists' estimates, 78.0 for the estimates based on tables (difference from cardiologists' estimates p less than 0.05) and 83.1 for the estimates based on computer calculations (p less than 0.01). Thus probability analysis incorporating sufficient detail can achieve a diagnostic accuracy comparable with that of cardiologists. Studies of the efficacy of probability analysis in patient care are warranted.

Abstract

To determine the effect of exercise myocardial scintigraphy with thallium-201 on diagnostic accuracy and the need for coronary angiography, consecutive patients with a variety of clinical presentations were identified. Clinical summaries, including a detailed history, physical examination, and complete data from a standard treadmill exercise test, were presented to 91 cardiologists. The cardiologists assessed the probability of coronary disease and the need for coronary angiography. They were then presented the results of thallium scintigraphy and revised their assessments if warranted. Scintigraphy significantly increased the cardiologists' diagnostic accuracy beyond that attained with other clinical information (p less than 0.0001). The change in accuracy varied from + 4% to + 20% in different patient groups, and was greatest in patients with atypical angina and a positive exercise ECG. Ratings of the need for coronary angiography changed from -13% to +21% in different patient groups. We conclude that exercise thallium scintigraphy can provide independent diagnostic information and influence the need for coronary angiography.

Abstract

Adults presenting with nephrotic syndrome conventionally undergo renal biopsy before therapy is administered, whereas children with nephrotic syndrome receive a therapeutic trial of corticosteroids without prior renal biopsy. These two approaches are compared here by means of decision analysis. The results indicate that an initial trial of corticosteroid therapy in the adult yields as many, or more, remissions, fewer complications, and lower mortality than does routine renal biopsy. A trial of corticosteroids is an acceptable first step in management of adults as well as children with nephrotic syndrome.